Stem cell science and regenerative medicine
Version of Record online: 11 FEB 2013
Copyright © 2013 WILEY Periodicals, Inc.
Special Issue: Stem Cells
Volume 35, Issue 3, pages 147–148, March 2013
How to Cite
Tam, P. P. L. and Pera, M. F. (2013), Stem cell science and regenerative medicine. Bioessays, 35: 147–148. doi: 10.1002/bies.201300003
- Issue online: 11 FEB 2013
- Version of Record online: 11 FEB 2013
Patrick Tam (left), Deputy Director of Children's Medical Research Institute (CMRI), Sydney and Martin Pera (right), Program Leader of Stem Cells Australia, Melbourne
The contributors to this special issue of BioEssays survey the progress of stem cell research towards clinical translation in regenerative medicine. Basic research in stem cell biology continues to open up new avenues for development of therapeutics, as the function of stem cells in tissue regeneration and repair becomes clearer. We are now in a position to forecast the utility of some recent development in the basic science of stem and tissue progenitor cells in translational research. Furthermore, pluripotent stem cells and their derivatives may be envisaged as experimental tools for functional genomics for personalized medicine, disease modeling for the exploration of pathogenic mechanisms, drug discovery and development, and screening therapeutic agents for evaluating efficacy and safety. This special issue covers challenges at the interface of laboratory research and regenerative medicine; these include making functional cells, ex vivo expansion of tissue stem cells, safety issues of tumorigenicity, immunogenicity, and genome aberrations, functional integration of stem cells into tissue, and design of homing means for stem cell-mediated delivery of therapeutic agents.
On the functional attributes of stem cells, Asli and Harvey highlight the pivotal role of inter-conversion of epithelial and mesenchymal cell phenotypes in cell fate decisions, reprogramming and cancer. The manipulation of these processes has already been shown to enhance cellular reprogramming, and these authors discuss how epithelial to mesenchymal transitions may be critical to repair of damage to the myocardium. For many tissues, the identification of stem cells and the definition of their role in repair remain challenging. Ninkovic and Götz point out that a better mechanistic comprehension of the regulation of the balance between gliogenesis and neurogenesis in the central nervous system might help to enhance repair of brain injury. Neurogenesis is limited to a few discrete brain regions, but gliogenesis, and its associated pathologies, is ubiquitous in the central nervous system. Could glial scarring be diverted into productive and reparative neurogenesis? Likewise, identification of putative stem cell populations in the lung is clarifying the endogenous processes of renewal and repair in that tissue and guiding efforts to drive pluripotent stem cell differentiation in this direction (Green et al.). Satellite cells were defined as the stem cell of skeletal muscle many years ago, but Bentzinger et al. highlight challenges to application of this knowledge to the repair of skeletal muscle. Though studies have progressed in the mouse, we still lack adequate knowledge of the progenitor cells in the human. Levesque et al. consider the stem cell niche as a therapeutic target, pointing out that hematopoietic stem cell mobilization provides a classical example of a newly minted concept of nichotherapy. A better understanding of how transplanted stem cells interact with the endogenous niche is likely to be critical to successful cell therapies.
Outside of regenerative medicine, induced pluripotent stem cells offer great potential for disease modeling, drug discovery, and toxicology. Pomp and Colman survey the achievements to date and the challenges facing this field, including the difficulties in modeling disease phenotype. Rajamohan et al. focus on applications of induced pluripotent stem cells in the heart, where the use of cardiomyocytes in drug screening is now a reality.
A number of contributors discuss specific applications in which stem cell therapy is already advanced clinically. Millard and Fisk consider the many current clinical trials of mesenchymal stem cells, which are recognized to function as delivery systems for factors that enhance endogenous cell survival and repair and modulate inflammation. The authors conclude that most benefits reported to date are modest, and highlight the provocative notion that exosomes, which are the transfer vehicle for most secreted factors, may replace mesenchymal stem cells as the ultimate therapeutic agent. Diederichs et al. review the current state of cell therapy for skeletal injuries, an area in which mesenchymal stem cells are undergoing extensive evaluation. Despite some years of work, the only therapeutic paradigm currently available in the clinic as standard of care is that of autologous chondrocyte implantation. Osei-Bempong et al. discuss the repair of the corneal epithelium and emerging alternatives to autologous grafts of corneal limbal tissue expanded ex vivo. Although autologous transplants have been used successfully for some time, the mechanism whereby the graft provides benefit is unknown. The understanding of limbal stem cells is still limited, but may provide clues for the improvement of transplantation or alternative cell therapies in future. Shibata and Shen examine current knowledge of cancer stem cells, and reveal how recent findings on heterogeneity of stem cell populations, arising from genetic diversity, pose tough challenges for therapy based on the stem cell concept. Murphy and Atala consider the daunting challenges facing efforts to assemble tissues into organs, and highlight some current approaches that might find wider applicability, in particular, the possibility of mimicking natural extracellular matrix scaffolds with synthetic materials. Hussein et al. focus on a particular challenge to the use of induced pluripotent stem cells in therapy, namely the acquisition of genetic damage in specific cell lines, and conclude that induced pluripotent stem cells do present more challenges than embryonic stem cells in this respect. Hematopoietic stem cells have been in clinical use for many years, however, as Csaszar and colleagues point out, the ex vivo expansion of these cells poses significant challenges from a bioengineering and economic point of view.
It is notable that most of the questions and challenges raised by our contributors would not even have been conceived of 10 years ago. Translational research, firmly grounded in basic biological studies of stem cells and tissue regeneration and repair, is rapidly moving cell-based therapy towards clinical trials for a number of disease indications. The outcomes of these initial clinical trials are likely to raise more questions than they could answer. However, there is great hope that they will point the way towards a productive focus of the laboratory research and the emergence of more refined and effective treatment options.