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World-first transplant of iPSC-derived epithelial cell sheet

Osaka University scientists have transplanted a sheet of corneal epithelial cells derived from iPSCs in a world-first. The patient was treated for corneal epithelial stem cell exhaustion.

Go to the profile of Freya Leask
Sep 03, 2019

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Go to the profile of James L. Sherley, M.D., Ph.D.

It's hard to know what to make of these reports.  For a tissue like the cornea, that has a substantial turnover rate of new epithelial cell production required for its function,  patching without providing renewing limbal stem cells will not be an effective therapy.  There are earlier studies reported of effective autologous transplantation of limbal stem cell-containing corneal fragments from one eye to another in the same patient to repair a severely damaged cornea.  These earlier studies certainly set the concept for corneal stem cell therapy; and this type of stem cell replacement therapy is only type so far to show potential efficacy beyond established  hematopoietic stem cell transplantation therapies.  The concern with the now optimistically reported work from Osaka University (details of which were not evident at the link provided with this RegMedNet article) is that it may not consider whether the iPSC-derived corneal sheets contain any limbal stem cells.  Given the embryonic-like development that has so far typified iPSC in vitro differentiation, the required postnatal limbal stem cells may not be present in the transplant, destining these transplants to have an inadequate, short-lived function.   In addition, as always, the threat of residual undifferentiated, tumorigenic iPSCs is ever-present along with the possible functional deficiencies due to the genetic and epigenetic defects that are characteristic of pluripotent stem cells and the differentiated cells derived from them.  Lots of issues to consider and address that should temper patient expectations, if not the vaulting optimism of media reports.

Go to the profile of Prof. Veerappan Muthukkaruppan Ph.D

Prof. VR. Muthukkaruppan Ph.D.

An interesting news item appeared in RegMedNet and also in Nature News about the transplantation of “iPSC-derived epithelial cell sheet” to treat a patient with limbal stem cell deficiency (LSCD).

 It is important to distinguish between the patients who require donor corneal transplantation for a range of corneal disorders and those who require grafting of limbal stem cells. Since the patient in this report is of the latter type, it is required to determine whether the iPSC–derived epithelial sheet contains limbal stem-like cells. In other words, transplantation of differentiated corneal epithelial cells will not be an effective therapy for LSCD. Therefore, it is required to device methods to convert iPSCs to tissue–specific adult stem cells which alone when successfully grafted will have the capacity both to self-renew so as to remain as quiescent stem cells and to generate differentiated progeny to maintain homeostasis of the respective tissue throughout life. In addition, the successful long-term recovery also depends on the presence of normal functional niche in the limbal stroma of the LSCD patient.

On the basis of our understanding on the Biology of adult ocular stem cells, it is our considered opinion that it is relevant to bring in the concept of postnatal tissue-specific stem cells (with self-renewal, non–tumorigenic properties) for using pluripotent stem cells in regenerative medicine.