Frontiers in Stem Cell and Regenerative Medicine Research

There has been a rapid increase in our understanding in the isolation, culture and application of mesenchymal stem cells (MSC). Despite an increased understanding of MSC biology and new avenues for in vivo application - the standardization of laboratory practices for MSC is lacking. One particular example is in the examination of safety issues in MSC in vivo implantation. The following review will explore the current laboratory practices for the safety assessments of MSC implantation, from diverse viewpoints of such as histopathology, cytopathology, and cytogenetics. A snapshot of current practices and techniques is presented across three common types of MSC differentiation: bone, cartilage, and muscle tissue. Overall, we uncovered a relative lack of investigation of safety issues in MSC implantation. For example, cell proliferation and local inflammation were only assessed in less than one third of manuscripts. Additionally, the average length of study was less than two weeks, a short period limited in its detection of adverse outcomes. The present review uncovers a relative paucity of papers that place emphasis on safety outcomes for animal studies. Given the potential role of MSC in sarcomagenesis and other tumorigenesis, the routine performance safety assays for MSC mediated tissue engineering studies will facilitate the future translation to clinical use. Finally, we provide a set of practical preliminary suggestions is presented for safety assessments in MSC implantation models. In summary, in order to bridge the gap in translation from animal to human, increased practice and routinization of safety assessments in MSC implantation will be beneficial.

Immunologic reconstitution is a critical component for successful outcome of haematopoietic stem cell transplantation. Chemotherapy and pre-transplant conditioning impairs thymic function leading to delayed T-cell regeneration and the increased risk of opportunistic infections and leukaemia relapse. Immune reconstitution can be promoted through administration of common γ-chain cytokines such as IL-2, IL-7 and IL-15. Prevention of thymic involution achieved by administration of keratinocyte growth factor, growth hormone and sex hormone inhibition has also been shown to improve immune reconstitution. Additionally, cell therapy that includes adoptive transfer of ex vivo generated T-cells or T-cell precursors, T-cells specific for viral or tumour antigens and, natural killer (NK) cells appears to be a promising therapeutic approach to improve immune reconstitution after transplantation. Pharmacological modulation of signalling pathways, such as Wnt and Notch, play an important role during different stages of Tcell development. Activation of Wnt signalling using small molecule inhibition of GSK3β was shown to promote post-transplant T-cell regeneration in pre-clinical models. The use of pharmaceutical agents to accelerate T-cell reconstitution and boost T-cell-mediated immunity in recipients of haematopoietic stem cell grafts warrants further investigation.

The additive effect of stem cell therapy and biomaterial substrates provides exciting opportunities for tissue engineering and regenerative medicine applications. Nanofibrous substrates can be fabricated to mimic the nano-architectural structure of specific, native tissue extracellular matrix. This provides topographical structure and contact guidance, which can impact stem cell biology as well as direct their differentiation towards specific lineages. This chapter highlights nanofibrous substrates as an alternative tool for the expansion and differentiation of embryonic stem cells. Future applications of such technology could promote the use of hESC-derived cells for clinical applications.

The cornea represents two thirds of the eye’s refractive power and, together with the sclera, is the protective shield of intraocular structures. The cornea is composed of three cellular layers (epithelium, stroma and endothelium) and three acellular layers (Bowman’s, Dua’s and Descemet’s). Corneal pathologies can affect one or all corneal layers, producing corneal opacities. Penetrating keratoplasty is currently being displaced by lamellar techniques that selectively replace the diseased layer, but neither solves the classical difficulties encountered in corneal transplantation, such as immune rejection and a shortage of organs. The development of bioengineered corneas composed of prosthetic or natural scaffolds and autologous stem cells that differentiate into corneal cells could overcome these difficulties.