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Current Stem Cell Research & Therapy

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ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

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Review Article

Secretome Derived from Mesenchymal Stem/Stromal Cells: A Promising Strategy for Diabetes and its Complications

Author(s): ling li, Siyu Hua, Lianghui You* and Tianying Zhong*

Volume 19, Issue 10, 2024

Published on: 17 October, 2023

Page: [1328 - 1350] Pages: 23

DOI: 10.2174/1574888X19666230913154544

Price: $65

Abstract

Diabetes is a complex metabolic disease with a high global prevalence. The health and quality of life of patients with diabetes are threatened by many complications, including diabetic foot ulcers, diabetic kidney diseases, diabetic retinopathy, and diabetic peripheral neuropathy. The application of mesenchymal stem/stromal cells (MSCs) in cell therapies has been recognized as a potential treatment for diabetes and its complications. MSCs were originally thought to exert biological effects exclusively by differentiating and replacing specific impaired cells. However, the paracrine function of factors secreted by MSCs may exert additional protective effects. MSCs secrete multiple compounds, including proteins, such as growth factors, chemokines, and other cytokines; nucleic acids, such as miRNAs; and lipids, extracellular vesicles (EVs), and exosomes (Exos). Collectively, these secreted compounds are called the MSC secretome, and usage of these chemicals in cell-free therapies may provide stronger effects with greater safety and convenience. Recent studies have demonstrated positive effects of the MSC secretome, including improved insulin sensitivity, reduced inflammation, decreased endoplasmic reticulum stress, enhanced M2 polarization of macrophages, and increased angiogenesis and autophagy; however, the mechanisms leading to these effects are not fully understood. This review summarizes the current research regarding the secretome derived from MSCs, including efforts to quantify effectiveness and uncover potential molecular mechanisms in the treatment of diabetes and related disorders. In addition, limitations and challenges are also discussed so as to facilitate applications of the MSC secretome as a cell-free therapy for diabetes and its complications.

Keywords: Mesenchymal stem cell/stromal cell, secretome, diabetes complications, exosome, miRNA, metabolic disease.

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[1]
Sun, H.; Saeedi, P.; Karuranga, S. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res. Clin. Pract., 2022, 183, 109119.
[http://dx.doi.org/10.1016/j.diabres.2021.109119] [PMID: 34879977]
[2]
Todd, J.A. Etiology of type 1 diabetes. Immunity, 2010, 32(4), 457-467.
[http://dx.doi.org/10.1016/j.immuni.2010.04.001] [PMID: 20412756]
[3]
Van Belle, T.L.; Coppieters, K.T.; Von Herrath, M.G. Type 1 diabetes: Etiology, immunology, and therapeutic strategies. Physiol. Rev., 2011, 91(1), 79-118.
[http://dx.doi.org/10.1152/physrev.00003.2010] [PMID: 21248163]
[4]
J D C. Diagnosis and classification of diabetes mellitus[J]. 2014, 81-90.
[5]
Kolb, H.; Mandrup-Poulsen, T. An immune origin of type 2 diabetes? Diabetologia, 2005, 48(6), 1038-1050.
[http://dx.doi.org/10.1007/s00125-005-1764-9] [PMID: 15864529]
[6]
Melendez-Ramirez, L.Y.; Richards, R.J.; Cefalu, W.T. Complications of type 1 diabetes. Endocrinol. Metab. Clin. North Am., 2010, 39(3), 625-640.
[http://dx.doi.org/10.1016/j.ecl.2010.05.009] [PMID: 20723824]
[7]
He, S.; Wang, J.; Zhang, X. Long-term influence of type 2 diabetes and metabolic syndrome on all-cause and cardiovascular death, and microvascular and macrovascular complications in Chinese adults — A 30-year follow-up of the Da Qing diabetes study. Diabetes Res. Clin. Pract., 2022, 191, 110048.
[http://dx.doi.org/10.1016/j.diabres.2022.110048] [PMID: 36029887]
[8]
Donath, M.Y.; Dinarello, C.A.; Mandrup-Poulsen, T. Targeting innate immune mediators in type 1 and type 2 diabetes. Nat. Rev. Immunol., 2019, 19(12), 734-746.
[http://dx.doi.org/10.1038/s41577-019-0213-9] [PMID: 31501536]
[9]
Huang, H.; Shang, Y.; Li, H. Co-transplantation of islets-laden microgels and biodegradable O 2 -generating microspheres for diabetes treatment. ACS Appl. Mater. Interfaces, 2022, 14(34), 38448-38458.
[http://dx.doi.org/10.1021/acsami.2c07215] [PMID: 35980755]
[10]
Horwitz, E.M.; Le Blanc, K.; Dominici, M. Clarification of the nomenclature for MSC: The international society for cellular therapy position statement. Cytotherapy, 2005, 7(5), 393-395.
[http://dx.doi.org/10.1080/14653240500319234] [PMID: 16236628]
[11]
Zhao, K.; Lin, R.; Fan, Z. Mesenchymal stromal cells plus basiliximab, calcineurin inhibitor as treatment of steroid-resistant acute graft-versus-host disease: A multicenter, randomized, phase 3, open-label trial. J. Hematol. Oncol., 2022, 15(1), 22.
[http://dx.doi.org/10.1186/s13045-022-01240-4] [PMID: 35255929]
[12]
Kim, H.J.; Cho, K.R.; Jang, H. Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: A phase I clinical trial. Alzheimers Res. Ther., 2021, 13(1), 154.
[http://dx.doi.org/10.1186/s13195-021-00897-2] [PMID: 34521461]
[13]
Barnhoorn, M.C.; Wasser, M.N.J.M.; Roelofs, H. Long-term evaluation of allogeneic bone marrow-derived mesenchymal stromal cell therapy for crohn’s disease perianal fistulas. J. Crohn’s Colitis, 2020, 14(1), 64-70.
[http://dx.doi.org/10.1093/ecco-jcc/jjz116] [PMID: 31197361]
[14]
Kassem, D.H.; Habib, S.A.; Badr, O.I. Isolation of rat adipose tissue mesenchymal stem cells for differentiation into insulin-producing cells. [J]. J Vis. Exp., 2022, 186.
[15]
Poursafavi, Z.; Abroun, S.; Kaviani, S.; Hayati Roodbari, N. Differentiation of alginate-encapsulated wharton jelly-derived mesenchymal stem cells into insulin producing cells. Cell J., 2022, 24(8), 449-457. [J
[PMID: 36093804]
[16]
Rodprasert, W.; Nantavisai, S.; Pathanachai, K.; Pavasant, P.; Osathanon, T.; Sawangmake, C. Tailored generation of insulin producing cells from canine mesenchymal stem cells derived from bone marrow and adipose tissue. Sci. Rep., 2021, 11(1), 12409.
[http://dx.doi.org/10.1038/s41598-021-91774-3] [PMID: 34117315]
[17]
Liang, R.Y.; Zhang, K.L.; Chuang, M.H. A one-step, monolayer culture and chemical-based approach to generate insulin-producing cells from human adipose-derived stem cells to mitigate hyperglycemia in STZ-induced diabetic rats. Cell Transplant., 2022, 31.
[http://dx.doi.org/10.1177/09636897221106995] [PMID: 36002988]
[18]
Kim, S.Y.; Kim, Y.R.; Park, W.J. Characterisation of insulin-producing cells differentiated from tonsil derived mesenchymal stem cells. Differentiation, 2015, 90(1-3), 27-39.
[http://dx.doi.org/10.1016/j.diff.2015.08.001] [PMID: 26391447]
[19]
Karagyaur, M.; Dzhauari, S.; Basalova, N. MSC secretome as a promising tool for neuroprotection and neuroregeneration in a model of intracerebral hemorrhage. Pharmaceutics, 2021, 13(12), 2031.
[http://dx.doi.org/10.3390/pharmaceutics13122031] [PMID: 34959314]
[20]
Park, H.; Chugh, R.M.; El Andaloussi, A. Human BM-MSC secretome enhances human granulosa cell proliferation and steroidogenesis and restores ovarian function in primary ovarian insufficiency mouse model. Sci. Rep., 2021, 11(1), 4525.
[http://dx.doi.org/10.1038/s41598-021-84216-7] [PMID: 33633319]
[21]
Eiro, N.; Fraile, M.; González-Jubete, A.; González, L.O.; Vizoso, F.J. Mesenchymal (Stem) stromal cells based as new therapeutic alternative in inflammatory bowel disease: Basic mechanisms, experimental and clinical evidence, and challenges. Int. J. Mol. Sci., 2022, 23(16), 8905.
[http://dx.doi.org/10.3390/ijms23168905] [PMID: 36012170]
[22]
Viswanathan, S.; Shi, Y.; Galipeau, J. Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy (ISCT®) Mesenchymal Stromal Cell committee position statement on nomenclature. Cytotherapy, 2019, 21(10), 1019-1024.
[http://dx.doi.org/10.1016/j.jcyt.2019.08.002] [PMID: 31526643]
[23]
Kawada-Horitani, E.; Kita, S.; Okita, T. Human adipose-derived mesenchymal stem cells prevent type 1 diabetes induced by immune checkpoint blockade. Diabetologia, 2022, 65(7), 1185-1197.
[http://dx.doi.org/10.1007/s00125-022-05708-3] [PMID: 35511238]
[24]
Liu, Y.; Chen, J.; Liang, H. Human umbilical cord-derived mesenchymal stem cells not only ameliorate blood glucose but also protect vascular endothelium from diabetic damage through a paracrine mechanism mediated by MAPK/ERK signaling. Stem Cell Res. Ther., 2022, 13(1), 258.
[http://dx.doi.org/10.1186/s13287-022-02927-8] [PMID: 35715841]
[25]
Sun, Y.L.; Shang, L.R.; Liu, R.H. Therapeutic effects of menstrual blood-derived endometrial stem cells on mouse models of streptozotocin-induced type 1 diabetes. World J. Stem Cells, 2022, 14(1), 104-116.
[http://dx.doi.org/10.4252/wjsc.v14.i1.104] [PMID: 35126831]
[26]
Elshemy, M.; Asem, M.; Allemailem, K. Antioxidative capacity of liver- and adipose-derived mesenchymal stem cell-conditioned media and their applicability in treatment of type 2. Diabetic Rats[J], 2021, 2021, 8833467.
[27]
Yin, Y.; Hao, H.; Cheng, Y. Human umbilical cord-derived mesenchymal stem cells direct macrophage polarization to alleviate pancreatic islets dysfunction in type 2 diabetic mice. Cell Death Dis., 2018, 9(7), 760.
[http://dx.doi.org/10.1038/s41419-018-0801-9] [PMID: 29988034]
[28]
Chahal, J.; Gómez-Aristizábal, A.; Shestopaloff, K. Bone marrow mesenchymal stromal cell treatment in patients with osteoarthritis results in overall improvement in pain and symptoms and reduces synovial inflammation. Stem Cells Transl. Med., 2019, 8(8), 746-757.
[http://dx.doi.org/10.1002/sctm.18-0183] [PMID: 30964245]
[29]
Baak, L.M.; Wagenaar, N.; van der Aa, N.E. Feasibility and safety of intranasally administered mesenchymal stromal cells after perinatal arterial ischaemic stroke in the Netherlands (PASSIoN): A first-in-human, open-label intervention study. Lancet Neurol., 2022, 21(6), 528-536.
[http://dx.doi.org/10.1016/S1474-4422(22)00117-X] [PMID: 35568047]
[30]
Izadi, M.; Sadr Hashemi Nejad, A.; Moazenchi, M. Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: A phase I/II randomized placebo-controlled clinical trial. Stem Cell Res. Ther., 2022, 13(1), 264.
[http://dx.doi.org/10.1186/s13287-022-02941-w] [PMID: 35725652]
[31]
Deng, D.; Zhang, P.; Guo, Y.; Lim, T.O. A randomised double-blind, placebo-controlled trial of allogeneic umbilical cord-derived mesenchymal stem cell for lupus nephritis. Ann. Rheum. Dis., 2017, 76(8), 1436-1439.
[http://dx.doi.org/10.1136/annrheumdis-2017-211073] [PMID: 28478399]
[32]
Clinicaltrialsgov 2022. Available From: https://www.clinicaltrials.gov/ (Accessed 24 October 2022).
[33]
Carlsson, P.O.; Schwarcz, E.; Korsgren, O.; Le Blanc, K. Preserved β-cell function in type 1 diabetes by mesenchymal stromal cells. Diabetes, 2015, 64(2), 587-592.
[http://dx.doi.org/10.2337/db14-0656] [PMID: 25204974]
[34]
Zang, L.; Li, Y.; Hao, H. Efficacy and safety of umbilical cord-derived mesenchymal stem cells in Chinese adults with type 2 diabetes: A single-center, double-blinded, randomized, placebo-controlled phase II trial. Stem Cell Res. Ther., 2022, 13(1), 180.
[http://dx.doi.org/10.1186/s13287-022-02848-6] [PMID: 35505375]
[35]
Zhang, C.; Huang, L.; Wang, X. Topical and intravenous administration of human umbilical cord mesenchymal stem cells in patients with diabetic foot ulcer and peripheral arterial disease: A phase I pilot study with a 3-year follow-up. Stem Cell Res. Ther., 2022, 13(1), 451.
[http://dx.doi.org/10.1186/s13287-022-03143-0] [PMID: 36064461]
[36]
Clinicaltrialsgov 2022. Available From: https://www.clinicaltrials.gov/ (Accessed 24 October 2022).
[37]
Chan, A.M.L.; Sampasivam, Y.; Lokanathan, Y. Biodistribution of mesenchymal stem cells (MSCs) in animal models and implied role of exosomes following systemic delivery of MSCs: A systematic review. Am. J. Transl. Res., 2022, 14(4), 2147-2161. [J
[PMID: 35559383]
[38]
Ammar, H.I.; Shamseldeen, A.M.; Shoukry, H.S. Metformin impairs homing ability and efficacy of mesenchymal stem cells for cardiac repair in streptozotocin-induced diabetic cardiomyopathy in rats. Am. J. Physiol. Heart Circ. Physiol., 2021, 320(4), H1290-H1302.
[http://dx.doi.org/10.1152/ajpheart.00317.2020] [PMID: 33513084]
[39]
Du, S.; Zeugolis, D.I.; O’Brien, T. Scaffold-based delivery of mesenchymal stromal cells to diabetic wounds. Stem Cell Res. Ther., 2022, 13(1), 426.
[http://dx.doi.org/10.1186/s13287-022-03115-4] [PMID: 35987712]
[40]
Nazarie Ignat, S.R.; Gharbia, S.; Hermenean, A.; Dinescu, S.; Costache, M. Regenerative potential of mesenchymal stem cells’ (MSCs) Secretome for liver fibrosis therapies. Int. J. Mol. Sci., 2021, 22(24), 13292.
[http://dx.doi.org/10.3390/ijms222413292] [PMID: 34948088]
[41]
Liao, H.J.; Chang, C.H.; Huang, C.Y.F.; Chen, H.T. Potential of using infrapatellar–fat–pad–derived mesenchymal stem cells for therapy in degenerative arthritis: Chondrogenesis, exosomes, and transcription regulation. Biomolecules, 2022, 12(3), 386.
[http://dx.doi.org/10.3390/biom12030386] [PMID: 35327578]
[42]
Delavogia, E.; Ntentakis, D.P.; Cortinas, J.A.; Fernandez-Gonzalez, A.; Alex Mitsialis, S.; Kourembanas, S. Mesenchymal stromal/stem cell extracellular vesicles and perinatal injury: One formula for many diseases. Stem Cells, 2022, 40(11), 991-1007.
[http://dx.doi.org/10.1093/stmcls/sxac062] [PMID: 36044737]
[43]
Asgari Taei, A.; Khodabakhsh, P.; Nasoohi, S.; Farahmandfar, M.; Dargahi, L. Paracrine effects of mesenchymal stem cells in ischemic stroke: Opportunities and challenges. Mol. Neurobiol., 2022, 59(10), 6281-6306.
[http://dx.doi.org/10.1007/s12035-022-02967-4] [PMID: 35922728]
[44]
An, T.; Chen, Y.; Tu, Y.; Lin, P. Mesenchymal stromal cell-derived extracellular vesicles in the treatment of diabetic foot ulcers: Application and challenges. Stem Cell Rev. Rep., 2021, 17(2), 369-378.
[http://dx.doi.org/10.1007/s12015-020-10014-9] [PMID: 32772239]
[45]
Deng, H.; Sun, C.; Sun, Y. Lipid, protein, and microRNA composition within mesenchymal stem cell-derived exosomes. Cell. Reprogram., 2018, 20(3), 178-186.
[http://dx.doi.org/10.1089/cell.2017.0047] [PMID: 29782191]
[46]
Bogatcheva, N.V.; Coleman, M.E. Conditioned medium of mesenchymal stromal cells: A new class of therapeutics. Biochemistry, 2019, 84(11), 1375-1389.
[http://dx.doi.org/10.1134/S0006297919110129] [PMID: 31760924]
[47]
Lui, P.P.Y.; Leung, Y.T. Practical considerations for translating mesenchymal stromal cell-derived extracellular vesicles from bench to bed. Pharmaceutics, 2022, 14(8), 1684.
[http://dx.doi.org/10.3390/pharmaceutics14081684] [PMID: 36015310]
[48]
Brunello, G.; Zanotti, F.; Trentini, M. Exosomes derived from dental pulp stem cells show different angiogenic and osteogenic properties in relation to the age of the donor. Pharmaceutics, 2022, 14(5), 908.
[http://dx.doi.org/10.3390/pharmaceutics14050908] [PMID: 35631496]
[49]
Wang, Y.; Zhang, L.; Wu, Y. Peptidome analysis of umbilical cord mesenchymal stem cell (hUC-MSC) conditioned medium from preterm and term infants. Stem Cell Res. Ther., 2020, 11(1), 414.
[http://dx.doi.org/10.1186/s13287-020-01931-0] [PMID: 32967723]
[50]
Seo, Y.; Shin, T.; Ahn, J. Human tonsil-derived mesenchymal stromal cells maintain proliferating and ros-regulatory properties via stanniocalcin-1. [J].Cells, 2020, 9(3), 636.
[51]
Bi, Y.; Qiao, X.; Liu, Q. Systemic proteomics and miRNA profile analysis of exosomes derived from human pluripotent stem cells. Stem Cell Res. Ther., 2022, 13(1), 449.
[http://dx.doi.org/10.1186/s13287-022-03142-1] [PMID: 36064647]
[52]
Pires, A.O.; Mendes-Pinheiro, B.; Teixeira, F.G. Unveiling the differences of secretome of human bone marrow mesenchymal stem cells, adipose tissue-derived stem cells, and human umbilical cord perivascular cells: A proteomic analysis. Stem Cells Dev., 2016, 25(14), 1073-1083.
[http://dx.doi.org/10.1089/scd.2016.0048] [PMID: 27226274]
[53]
Konala, V.B.R.; Bhonde, R.; Pal, R. Secretome studies of mesenchymal stromal cells (MSCs) isolated from three tissue sources reveal subtle differences in potency. In Vitro Cell. Dev. Biol. Anim., 2020, 56(9), 689-700.
[http://dx.doi.org/10.1007/s11626-020-00501-1] [PMID: 33006709]
[54]
Wang, S.; Umrath, F.; Cen, W.; Salgado, A.J.; Reinert, S.; Alexander, D. Pre-conditioning with IFN-γ and hypoxia enhances the angiogenic potential of iPSC-Derived MSC Secretome. Cells, 2022, 11(6), 988.
[http://dx.doi.org/10.3390/cells11060988] [PMID: 35326438]
[55]
Widjaja, S.L.; Salimo, H.; Yulianto, I. Soetrisno. Proteomic analysis of hypoxia and non-hypoxia secretome mesenchymal stem-like cells from human breastmilk. Saudi J. Biol. Sci., 2021, 28(8), 4399-4407.
[http://dx.doi.org/10.1016/j.sjbs.2021.04.034] [PMID: 34354424]
[56]
Zhang, B.; Tian, X.; Qu, Z.; Hao, J.; Zhang, W. Hypoxia-preconditioned extracellular vesicles from mesenchymal stem cells improve cartilage repair in osteoarthritis. Membranes, 2022, 12(2), 225.
[http://dx.doi.org/10.3390/membranes12020225] [PMID: 35207146]
[57]
Even, K.M.; Gaesser, A.M.; Ciamillo, S.A.; Linardi, R.L.; Ortved, K.F. Comparing the immunomodulatory properties of equine BM-MSCs culture expanded in autologous platelet lysate, pooled platelet lysate, equine serum and fetal bovine serum supplemented culture media. Front. Vet. Sci., 2022, 9, 958724.
[http://dx.doi.org/10.3389/fvets.2022.958724] [PMID: 36090170]
[58]
Asgari Taei, A.; Dargahi, L.; Khodabakhsh, P.; Kadivar, M.; Farahmandfar, M. Hippocampal neuroprotection mediated by secretome of human mesenchymal stem cells against experimental stroke. CNS Neurosci. Ther., 2022, 28(9), 1425-1438.
[http://dx.doi.org/10.1111/cns.13886] [PMID: 35715988]
[59]
Papait, A.; Ragni, E.; Cargnoni, A. Comparison of EV-free fraction, EVs, and total secretome of amniotic mesenchymal stromal cells for their immunomodulatory potential: A translational perspective. Front. Immunol., 2022, 13, 960909.
[http://dx.doi.org/10.3389/fimmu.2022.960909] [PMID: 36052081]
[60]
Lin, H.; Chen, H.; Zhao, X. Advances in mesenchymal stem cell conditioned medium-mediated periodontal tissue regeneration. J. Transl. Med., 2021, 19(1), 456.
[http://dx.doi.org/10.1186/s12967-021-03125-5] [PMID: 34736500]
[61]
Sun, X.; Li, K.; Aryal, U.K.; Li, B.Y.; Yokota, H. PI3K-activated MSC proteomes inhibit mammary tumors via Hsp90ab1 and Myh9. Mol. Ther. Oncolytics, 2022, 26, 360-371.
[http://dx.doi.org/10.1016/j.omto.2022.08.003] [PMID: 36090473]
[62]
Tan, H.L.; Guan, X.H.; Hu, M. Human amniotic mesenchymal stem cells-conditioned medium protects mice from high-fat diet-induced obesity. Stem Cell Res. Ther., 2021, 12(1), 364.
[http://dx.doi.org/10.1186/s13287-021-02437-z] [PMID: 34174964]
[63]
Obendorf, J.; Fabian, C.; Thome, U.H.; Laube, M. Paracrine stimulation of perinatal lung functional and structural maturation by mesenchymal stem cells. Stem Cell Res. Ther., 2020, 11(1), 525.
[http://dx.doi.org/10.1186/s13287-020-02028-4] [PMID: 33298180]
[64]
Huang, J; U KP; Yang, F Human pluripotent stem cell-derived ectomesenchymal stromal cells promote more robust functional recovery than umbilical cord-derived mesenchymal stromal cells after hypoxic-ischaemic brain damage. Theranostics, 2022, 12(1), 143-166.
[http://dx.doi.org/10.7150/thno.57234] [PMID: 34987639]
[65]
De Gregorio, C.; Contador, D.; Díaz, D. Human adipose-derived mesenchymal stem cell-conditioned medium ameliorates polyneuropathy and foot ulceration in diabetic BKS db/db mice. Stem Cell Res. Ther., 2020, 11(1), 168.
[66]
Chen, H.; Zhang, H.; Zheng, Y. Prolyl hydroxylase 2 silencing enhances the paracrine effects of mesenchymal stem cells on necrotizing enterocolitis in an NF-κB-dependent mechanism. Cell Death Dis., 2020, 11(3), 188.
[http://dx.doi.org/10.1038/s41419-020-2378-3] [PMID: 32179740]
[67]
Ti, D.; Hao, H.; Tong, C. LPS-preconditioned mesenchymal stromal cells modify macrophage polarization for resolution of chronic inflammation via exosome-shuttled let-7b. J. Transl. Med., 2015, 13, 308.
[68]
Elshaer, S.; Evans, W.; Pentecost, M. Adipose stem cells and their paracrine factors are therapeutic for early retinal complications of diabetes in the Ins2 mouse[J]. Stem Cell Res. Ther., 2018, 9(1), 322.
[69]
Liu, W.; Yu, M.; Xie, D. Melatonin-stimulated MSC-derived exosomes improve diabetic wound healing through regulating macrophage M1 and M2 polarization by targeting the PTEN/AKT pathway. Stem Cell Res. Ther., 2020, 11(1), 259.
[http://dx.doi.org/10.1186/s13287-020-01756-x] [PMID: 32600435]
[70]
Shao, H.; Im, H.; Castro, C.M.; Breakefield, X.; Weissleder, R.; Lee, H. New technologies for analysis of extracellular vesicles. Chem. Rev., 2018, 118(4), 1917-1950.
[http://dx.doi.org/10.1021/acs.chemrev.7b00534] [PMID: 29384376]
[71]
Hade, M.D.; Suire, C.N.; Mossell, J.; Suo, Z. Extracellular vesicles: Emerging frontiers in wound healing. Med. Res. Rev., 2022, 42(6), 2102-2125.
[http://dx.doi.org/10.1002/med.21918] [PMID: 35757979]
[72]
Kahmini, F.R.; Shahgaldi, S. Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles as novel cell-free therapy for treatment of autoimmune disorders. Exp. Mol. Pathol., 2021, 118, 104566.
[http://dx.doi.org/10.1016/j.yexmp.2020.104566] [PMID: 33160961]
[73]
Lin, Z.; Wu, Y.; Xu, Y.; Li, G.; Li, Z.; Liu, T. Mesenchymal stem cell-derived exosomes in cancer therapy resistance: Recent advances and therapeutic potential. Mol. Cancer, 2022, 21(1), 179.
[http://dx.doi.org/10.1186/s12943-022-01650-5] [PMID: 36100944]
[74]
Karami fath, M; Anjomrooz, M; Taha, SR The therapeutic effect of exosomes from mesenchymal stem cells on colorectal cancer: Toward cell-free therapy. Pathol Res Pract, 2022, 237, 154024.
[http://dx.doi.org/10.1016/j.prp.2022.154024] [PMID: 35905664]
[75]
Wei, H.; Chen, F.; Chen, J. Mesenchymal stem cell derived exosomes as nanodrug carrier of doxorubicin for targeted osteosarcoma therapy via SDF1-CXCR4 Axis. Int. J. Nanomedicine, 2022, 17, 3483-3495.
[http://dx.doi.org/10.2147/IJN.S372851] [PMID: 35959282]
[76]
Su, Y.; Silva, J.D.; Doherty, D. Mesenchymal stromal cells-derived extracellular vesicles reprogramme macrophages in ARDS models through the miR-181a-5p-PTEN-pSTAT5-SOCS1 axis. Thorax, 2022, 78(6), 617-630.
[PMID: 35948417]
[77]
Ma, X.; Wang, Y.; Shi, Y. Exosomal miR-132-3p from mesenchymal stromal cells improves synaptic dysfunction and cognitive decline in vascular dementia. Stem Cell Res. Ther., 2022, 13(1), 315.
[http://dx.doi.org/10.1186/s13287-022-02995-w] [PMID: 35841005]
[78]
He, Q.; Wang, L.; Zhao, R. Retracted article: Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy. Stem Cell Res. Ther., 2020, 11(1), 223.
[http://dx.doi.org/10.1186/s13287-020-01731-6] [PMID: 32513303]
[79]
Ebrahim, N.; Ahmed, I.; Hussien, N. Mesenchymal stem cell-derived exosomes ameliorated diabetic nephropathy by autophagy induction through the mtor signaling pathway. Cells, 2018, 7(12), 226.
[80]
Li, B.; Luan, S.; Chen, J. The MSC-Derived exosomal lncRNA H19 promotes wound healing in diabetic foot ulcers by upregulating PTEN via MicroRNA-152-3p. Mol. Ther. Nucleic Acids, 2020, 19, 814-826.
[http://dx.doi.org/10.1016/j.omtn.2019.11.034] [PMID: 31958697]
[81]
Chen, Y.; Ding, H.; Wei, M. MSC-Secreted exosomal H19 promotes trophoblast cell invasion and migration by downregulating let-7b and upregulating FOXO1. Mol. Ther. Nucleic Acids, 2020, 19, 1237-1249.
[http://dx.doi.org/10.1016/j.omtn.2019.11.031] [PMID: 32069774]
[82]
Zhang, Q.; Cao, L.; Zou, S. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles carrying MicroRNA-181c-5p Promote BMP2-Induced repair of cartilage injury through inhibition of SMAD7 expression. Stem Cells Int., 2022, 2022, 1-14.
[http://dx.doi.org/10.1155/2022/1157498] [PMID: 35782228]
[83]
Yin, S.; Liu, W.; Ji, C. hucMSC-sEVs-Derived 14-3-3ζ serves as a bridge between yap and autophagy in diabetic kidney disease. Oxid. Med. Cell. Longev., 2022, 2022, 1-18.
[http://dx.doi.org/10.1155/2022/3281896] [PMID: 36199425]
[84]
Garcia, S.G.; Sandoval-Hellín, N.; Clos-Sansalvador, M. Mesenchymal stromal cells induced regulatory B cells are enriched in extracellular matrix genes and IL-10 independent modulators. Front. Immunol., 2022, 13, 957797.
[http://dx.doi.org/10.3389/fimmu.2022.957797] [PMID: 36189264]
[85]
Jiang, Y.; Hong, S.; Zhu, X. IL-10 partly mediates the ability of MSC-derived extracellular vesicles to attenuate myocardial damage in experimental metabolic renovascular hypertension. Front. Immunol., 2022, 13, 940093.
[http://dx.doi.org/10.3389/fimmu.2022.940093] [PMID: 36203611]
[86]
Lu, T.; Zhang, J.; Cai, J. Extracellular vesicles derived from mesenchymal stromal cells as nanotherapeutics for liver ischaemia–reperfusion injury by transferring mitochondria to modulate the formation of neutrophil extracellular traps. Biomaterials, 2022, 284, 121486.
[http://dx.doi.org/10.1016/j.biomaterials.2022.121486] [PMID: 35447404]
[87]
Nickel, S.; Christ, M.; Schmidt, S. Human mesenchymal stromal cells resolve lipid load in high fat diet-induced non-alcoholic steatohepatitis in mice by mitochondria donation. Cells, 2022, 11(11), 1829.
[http://dx.doi.org/10.3390/cells11111829] [PMID: 35681524]
[88]
Hashemi, S.; Hassan, Z.; Hossein-Khannazer, N. Investigating the route of administration and efficacy of adipose tissue-derived mesenchymal stem cells and conditioned medium in type 1 diabetic mice. Inflammopharmacology, 2020, 28(2), 585-601.
[89]
Cooper, T; Sherman, S; Bell, G Ultrafiltration and injection of islet regenerative stimuli secreted by pancreatic mesenchymal stromal cells[J] 2021, 30(5), 247-64.
[90]
Gao, X.; Song, L.; Shen, K. Bone marrow mesenchymal stem cells promote the repair of islets from diabetic mice through paracrine actions. Mol. Cell. Endocrinol., 2014, 338(1-2), 41-50.
[91]
Nojehdehi, S.; Soudi, S.; Hesampour, A.; Rasouli, S.; Soleimani, M.; Hashemi, S.M. Immunomodulatory effects of mesenchymal stem cell–derived exosomes on experimental type‐1 autoimmune diabetes. J. Cell. Biochem., 2018, 119(11), 9433-9443.
[http://dx.doi.org/10.1002/jcb.27260] [PMID: 30074271]
[92]
Keshtkar, S.; Kaviani, M.; Sarvestani, F.S. Exosomes derived from human mesenchymal stem cells preserve mouse islet survival and insulin secretion function. EXCLI J., 2020, 19, 1064-1080. [J
[PMID: 33013264]
[93]
Alkaabi, J.; Sharma, C.; Yasin, J. Relationship between lipid profile, inflammatory and endothelial dysfunction biomarkers, and type 1 diabetes mellitus: A case-control study. Am. J. Transl. Res., 2022, 14(7), 4838-4847. [J
[PMID: 35958469]
[94]
Hu, X.F.; Xiang, G.; Wang, T.J. Impairment of type H vessels by NOX2-mediated endothelial oxidative stress: Critical mechanisms and therapeutic targets for bone fragility in streptozotocin-induced type 1 diabetic mice. Theranostics, 2021, 11(8), 3796-3812.
[http://dx.doi.org/10.7150/thno.50907] [PMID: 33664862]
[95]
Clinicaltrialsgov 2022. Available From: https://www.clinicaltrials.gov/ (Accessed 24 October 2022).
[96]
Gao, D.; Jiao, J.; Wang, Z. The roles of cell-cell and organ-organ crosstalk in the type 2 diabetes mellitus associated inflammatory microenvironment. Cytokine Growth Factor Rev., 2022, 66, 15-25.
[http://dx.doi.org/10.1016/j.cytogfr.2022.04.002] [PMID: 35459618]
[97]
Bhatti, J.S.; Sehrawat, A.; Mishra, J. Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives. Free Radic. Biol. Med., 2022, 184, 114-134.
[http://dx.doi.org/10.1016/j.freeradbiomed.2022.03.019] [PMID: 35398495]
[98]
Polovina, M.M.; Potpara, T.S. Endothelial dysfunction in metabolic and vascular disorders. Postgrad. Med., 2014, 126(2), 38-53.
[http://dx.doi.org/10.3810/pgm.2014.03.2739] [PMID: 24685967]
[99]
Yuan, Y.; Shi, M.; Li, L. Mesenchymal stem cell-conditioned media ameliorate diabetic endothelial dysfunction by improving mitochondrial bioenergetics via the Sirt1/AMPK/PGC-1α pathway. Clin. Sci., 2016, 130(23), 2181-2198.
[http://dx.doi.org/10.1042/CS20160235] [PMID: 27613156]
[100]
Sanap, A.; Bhonde, R.; Joshi, K. Conditioned medium of adipose derived mesenchymal stem cells reverse insulin resistance through downregulation of stress induced serine kinases. Eur. J. Pharmacol., 2020, 881, 173215.
[http://dx.doi.org/10.1016/j.ejphar.2020.173215] [PMID: 32473166]
[101]
Kim, H.J.; Li, Q.; Song, W.J. Fibroblast growth factor-1 as a mediator of paracrine effects of canine adipose tissue-derived mesenchymal stem cells on in vitro-induced insulin resistance models. BMC Vet. Res., 2018, 14(1), 351.
[http://dx.doi.org/10.1186/s12917-018-1671-1] [PMID: 30445954]
[102]
Shree, N.; Bhonde, R.R. Conditioned media from adipose tissue derived mesenchymal stem cells reverse insulin resistance in cellular models. J. Cell. Biochem., 2017, 118(8), 2037-2043.
[http://dx.doi.org/10.1002/jcb.25777] [PMID: 27791278]
[103]
Kim, K.S.; Choi, Y.K.; Kim, M.J. Umbilical cord-mesenchymal stem cell-conditioned medium improves insulin resistance in C2C12 Cell. Diabetes Metab. J., 2021, 45(2), 260-269.
[http://dx.doi.org/10.4093/dmj.2019.0191] [PMID: 32662257]
[104]
Sun, Y.; Shi, H.; Yin, S. Human mesenchymal stem cell derived exosomes alleviate type 2 diabetes mellitus by reversing peripheral insulin resistance and relieving β-Cell destruction. ACS Nano, 2018, 12(8), 7613-7628.
[http://dx.doi.org/10.1021/acsnano.7b07643] [PMID: 30052036]
[105]
Liu, Z.; Han, J.; Wang, Y.; Yang, M.; Niu, L.; Shi, B. Association of serum C1Q/TNF-related protein 4 levels with carotid atherosclerosis in subjects with type 2 diabetes mellitus: A cross-sectional study. Clin. Chim. Acta, 2022, 531, 337-341.
[http://dx.doi.org/10.1016/j.cca.2022.04.1004] [PMID: 35525266]
[106]
Riveline, J.; Vergés, B.; Detournay, B. Design of a prospective, longitudinal cohort of people living with type 1 diabetes exploring factors associated with the residual cardiovascular risk and other diabetes-related complications: The SFDT1 study. Diabetes Metab., 2022, 48(3), 101306.
[http://dx.doi.org/10.1016/j.diabet.2021.101306] [PMID: 34813929]
[107]
Sela, Y.; Grinberg, K.; Cukierman-Yaffe, T.; Natovich, R. Relationship between cognitive function in individuals with diabetic foot ulcer and mortality. Diabetol. Metab. Syndr., 2022, 14(1), 133.
[http://dx.doi.org/10.1186/s13098-022-00901-1] [PMID: 36123752]
[108]
Lytvyn, Y.; Albakr, R.; Bjornstad, P. Renal hemodynamic dysfunction and neuropathy in longstanding type 1 diabetes: Results from the Canadian study of longevity in type 1 diabetes. J. Diabetes Complications, 2022, 36(11), 108320.
[http://dx.doi.org/10.1016/j.jdiacomp.2022.108320] [PMID: 36201892]
[109]
Li, X.Y.; Zhang, X.T.; Jiao, Y.C. In vivo evaluation and mechanism prediction of anti-diabetic foot ulcer based on component analysis of Ruyi Jinhuang powder. World J. Diabetes, 2022, 13(8), 622-642.
[http://dx.doi.org/10.4239/wjd.v13.i8.622] [PMID: 36159224]
[110]
Tuglo, L.S. Prevalence and determinants of lower extremity amputations among type I and type II diabetic patients: A multicenter-based study. Int. Wound J., 2022, 20(4), 903-909.
[PMID: 36054437]
[111]
Pastar, I.; Balukoff, N.C.; Marjanovic, J. Molecular pathophysiology of chronic wounds: Current state and future directions. Cold Spring Harb. Perspect. Biol., 2022, 15(4), a041243.
[PMID: 36123031]
[112]
Huang, J.; Zhang, S.; Ding, X. Research progress on the mechanism by which skin macrophage dysfunction mediates chronic inflammatory injury in diabetic skin. Front. Endocrinol., 2022, 13, 960551.
[http://dx.doi.org/10.3389/fendo.2022.960551] [PMID: 36093074]
[113]
Gao, D.; Xie, J.; Zhang, J. MSC attenuate diabetes-induced functional impairment in adipocytes via secretion of insulin-like growth factor-1. Biochem. Biophys. Res. Commun., 2014, 452(1), 99-105.
[http://dx.doi.org/10.1016/j.bbrc.2014.08.060] [PMID: 25152396]
[114]
You, H.; Namgoong, S.; Han, S. Wound-healing potential of human umbilical cord blood-derived mesenchymal stromal cells in vitro-a pilot study [J]. Cytotherapy, 2015, 17(11), 1506-1513. [J
[115]
Kinoshita, K.; Kuno, S.; Ishimine, H. Therapeutic potential of adipose-derived SSEA-3-Positive muse cells for treating diabetic skin ulcers. Stem Cells Transl. Med., 2015, 14(2), 146-155.
[116]
Kato, Y.; Iwata, T.; Morikawa, S. Allogeneic transplantation of an adipose-derived stem cell sheet combined with artificial skin accelerates wound healing in a rat wound model of type 2 diabetes and obesity. Diabetes, 2015, 64(8), 2723-2734.
[117]
De Mayo, T.; Conget, P.; Becerra-Bayona, S. The role of bone marrow mesenchymal stromal cell derivatives in skin wound healing in diabetic mice. PLoS One, 2017, 12(6), e0177533.
[118]
Bailey, A.; Li, H.; Kirkham, A. MSC-Derived Extracellular Vesicles to heal diabetic wounds: A systematic review and meta-analysis of preclinical animal studies. Stem Cell Rev. Rep., 2022, 18(3), 968-979.
[119]
Yu, M.; Liu, W.; Li, J. Exosomes derived from atorvastatin-pretreated MSC accelerate diabetic wound repair by enhancing angiogenesis via AKT/eNOS pathway. Stem Cell Res. Ther., 2020, 11(1), 350.
[http://dx.doi.org/10.1186/s13287-020-01824-2] [PMID: 32787917]
[120]
Pomatto, M.; Gai, C.; Negro, F. Differential therapeutic effect of extracellular vesicles derived by bone marrow and adipose mesenchymal stem cells on wound healing of diabetic ulcers and correlation to their cargoes. Int. J. Mol. Sci., 2021, 22(8), 3851.
[http://dx.doi.org/10.3390/ijms22083851] [PMID: 33917759]
[121]
Hu, J.; Liu, X.; Chi, J. Resveratrol enhances wound healing in type 1 diabetes mellitus by promoting the expression of extracellular vesicle-carried MicroRNA-129 derived from mesenchymal stem cells. J. Proteome Res., 2022, 21(2), 313-324.
[122]
Karalliedde, J.; Winocour, P.; Chowdhury, T.A. Clinical practice guidelines for management of hyperglycaemia in adults with diabetic kidney disease. Diabet. Med., 2022, 39(4), e14769.
[http://dx.doi.org/10.1111/dme.14769] [PMID: 35080257]
[123]
Inker, L.A.; Astor, B.C.; Fox, C.H. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am. J. Kidney Dis., 2014, 63(5), 713-735.
[http://dx.doi.org/10.1053/j.ajkd.2014.01.416] [PMID: 24647050]
[124]
Li, H.; Rong, P.; Ma, X. Mouse umbilical cord mesenchymal stem cell paracrine alleviates renal fibrosis in diabetic nephropathy by reducing myofibroblast transdifferentiation and cell proliferation and upregulating mmps in mesangial cells[J]. J. Diabetes Res., 2020, 2020, 3847171.
[125]
Lv, S.; Liu, G.; Sun, A. Mesenchymal stem cells ameliorate diabetic glomerular fibrosis in vivo and in vitro by inhibiting TGF-β signalling via secretion of bone morphogenetic protein 7. Diab. Vasc. Dis. Res., 2014, 11(4), 251-261.
[126]
Lv, S.; Cheng, J.; Sun, A. Mesenchymal stem cells transplantation ameliorates glomerular injury in streptozotocin-induced diabetic nephropathy in rats via inhibiting oxidative stress. Diabetes Res. Clin. Pract., 2014, 104(1), 143-154.
[127]
Xiang, E.; Han, B.; Zhang, Q. Human umbilical cord-derived mesenchymal stem cells prevent the progression of early diabetic nephropathy through inhibiting inflammation and fibrosis. Stem Cell Res. Ther., 2020, 11(1), 336.
[128]
Bai, Y.; Wang, J.; He, Z. Mesenchymal stem cells reverse diabetic nephropathy disease via lipoxin a4 by targeting transforming growth factor β (tgf-β)/smad pathway and pro-inflammatory cytokines. Med. Sci. Monit., 2019, 25, 3069-3076.
[129]
Konari, N.; Nagaishi, K.; Kikuchi, S. Mitochondria transfer from mesenchymal stem cells structurally and functionally repairs renal proximal tubular epithelial cells in diabetic nephropathy in vivo. Sci. Rep., 2019, 9(1), 5184.
[130]
Park, J.; Hwang, I.; Hwang, S. Human umbilical cord blood-derived mesenchymal stem cells prevent diabetic renal injury through paracrine action. Diabetes Res. Clin. Pract., 2012, 98(3), 465-473.
[131]
Nagaishi, K.; Mizue, Y.; Chikenji, T. Mesenchymal stem cell therapy ameliorates diabetic nephropathy via the paracrine effect of renal trophic factors including exosomes. Sci. Rep., 2016, 6(1), 34842.
[http://dx.doi.org/10.1038/srep34842] [PMID: 27721418]
[132]
Grange, C.; Tritta, S.; Tapparo, M. Stem cell-derived extracellular vesicles inhibit and revert fibrosis progression in a mouse model of diabetic nephropathy. Sci. Rep., 2019, 9(1), 4468.
[133]
Hao, Y.; Miao, J.; Liu, W. Mesenchymal stem cell-derived exosomes carry microRNA-125a to protect against diabetic nephropathy by targeting histone deacetylase 1 and downregulating endothelin-1. Diabetes Metab. Syndr. Obes., 2021, 14, 1405-1418.
[134]
Zhong, L.; Liao, G.; Wang, X. Mesenchymal stem cells–microvesicle-miR-451a ameliorate early diabetic kidney injury by negative regulation of P15 and P19. Exp. Biol. Med., 2018, 243(15-16), 1233-1242.
[http://dx.doi.org/10.1177/1535370218819726] [PMID: 30614256]
[135]
Zhang, Y.; Le, X.; Zheng, S. MicroRNA-146a-5p-modified human umbilical cord mesenchymal stem cells enhance protection against diabetic nephropathy in rats through facilitating M2 macrophage polarization. Stem Cell Res. Ther., 2022, 13(1), 171.
[136]
Cai, X.; Zou, F.; Xuan, R. Exosomes from mesenchymal stem cells expressing microribonucleic acid-125b inhibit the progression of diabetic nephropathy via the tumour necrosis factor receptor-associated factor 6/Akt axis. Endocr. J., 2021, 68(7), 817-828.
[137]
McGurnaghan, S.J.; Blackbourn, L.A.K.; Caparrotta, T.M. Cohort profile: The Scottish diabetes research network national diabetes cohort – a population-based cohort of people with diabetes in scotland. BMJ Open, 2022, 12(10), e063046.
[http://dx.doi.org/10.1136/bmjopen-2022-063046] [PMID: 36223968]
[138]
Blonde, L.; Umpierrez, G.E.; Reddy, S.S. American association of clinical endocrinology clinical practice guideline: Developing a diabetes mellitus comprehensive care plan—2022 update. Endocr. Pract., 2022, 28(10), 923-1049.
[http://dx.doi.org/10.1016/j.eprac.2022.08.002] [PMID: 35963508]
[139]
Omori, K.; Nagata, N.; Kurata, K. Inhibition of stromal cell–derived factor-1α/CXCR4 signaling restores the blood-retina barrier in pericyte-deficient mouse retinas. JCI Insight, 2018, 3(23), e120706.
[http://dx.doi.org/10.1172/jci.insight.120706] [PMID: 30518679]
[140]
Yao, J.; Wu, X.; Yu, Q. The requirement of phosphoenolpyruvate carboxykinase 1 for angiogenesis in vitro and in vivo. Sci. Adv., 2022, 8(21), eabn6928.
[http://dx.doi.org/10.1126/sciadv.abn6928] [PMID: 35622925]
[141]
Song, J.; Huang, B.B.; Ong, J.X.; Konopek, N.; Fawzi, A.A. Hemodynamic effects of anti-vascular endothelial growth factor injections on optical coherence tomography angiography in diabetic macular edema eyes. Transl. Vis. Sci. Technol., 2022, 11(10), 5.
[http://dx.doi.org/10.1167/tvst.11.10.5] [PMID: 36180027]
[142]
Cheng, Y.; Du, Y.; Liu, H.; Tang, J.; Veenstra, A.; Kern, T.S. Photobiomodulation inhibits long-term structural and functional lesions of diabetic retinopathy. Diabetes, 2018, 67(2), 291-298.
[http://dx.doi.org/10.2337/db17-0803] [PMID: 29167189]
[143]
Zhang, W.; Wang, Y.; Kong, Y.J.I.O. Exosomes derived from mesenchymal stem cells modulate miR-126 to ameliorate hyperglycemia-induced retinal inflammation via targeting HMGB1. Invest. Ophthalmol. Vis. Sci., 2019, 60(1), 294-303.
[144]
Li, W.; Jin, L.; Cui, Y. Bone marrow mesenchymal stem cells-induced exosomal microRNA-486-3p protects against diabetic retinopathy through TLR4/NF-κB axis repression. J. Endocrinol. Invest., 2021, 44(6), 1193-1207.
[145]
Safwat, A.; Sabry, D.; Ragiae, A. Adipose mesenchymal stem cells-derived exosomes attenuate retina degeneration of streptozotocin-induced diabetes in rabbits. J. Circ. Biomark., 2018, 7, 1849454418807827.
[146]
Cao, X.; Xue, L.D.; Di, Y.; Li, T.; Tian, Y.J.; Song, Y. MSC-derived exosomal lncRNA SNHG7 suppresses endothelial-mesenchymal transition and tube formation in diabetic retinopathy via miR-34a-5p/XBP1 axis. Life Sci., 2021, 272, 119232.
[http://dx.doi.org/10.1016/j.lfs.2021.119232] [PMID: 33600866]
[147]
Sun, F.; Sun, Y.; Zhu, J. Mesenchymal stem cells-derived small extracellular vesicles alleviate diabetic retinopathy by delivering NEDD4. Stem Cell Res. Ther., 2022, 13(1), 293.
[http://dx.doi.org/10.1186/s13287-022-02983-0] [PMID: 35841055]
[148]
Clinicaltrialsgov 2022. Available From: https://www.clinicaltrials.gov/ (Accessed 24 October 2022).
[149]
Clinicaltrialsgov 2022. Available From: https://www.clinicaltrials.gov/ (Accessed 24 October 2022).
[150]
Abdelrahman, S.; Samak, M.; Shalaby, S.J.C. Fluoxetine pretreatment enhances neurogenic, angiogenic and immunomodulatory effects of MSCs on experimentally induced diabetic neuropathy. Cell Tissue Res., 2018, 374(1), 83-97.
[151]
Luo, R.; Li, L.; Liu, X. Mesenchymal stem cells alleviate palmitic acid-induced endothelial-to-mesenchymal transition by suppressing endoplasmic reticulum stress. Am. J. Physiol. Endocrinol. Metab., 2020, 319(6), 961-980.
[152]
Fan, B.; Li, C.; Szalad, A. Mesenchymal stromal cell-derived exosomes ameliorate peripheral neuropathy in a mouse model of diabetes. Diabetologia, 2020, 63(2), 431-433.

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