The prospect of induced pluripotent stem cells for diabetes mellitus treatment

Abstract

A continuous search for a permanent cure for diabetes mellitus is underway with several remarkable discoveries over the past few decades. One of these is the potential of pancreatic stem/progenitor cells to rejuvenate functional β cells. However, the existence of these cell populations is still obscure and a lack of phenotype characterization hampers their use in clinical settings. Cellular reprogramming through induced pluripotent stem (iPS) cell technology can become an alternative strategy to generate insulin-producing cells in a relatively safe (autologous-derived cells, thus devoid of rejection risk) and efficient way (high cellular proliferation) but retain a precise morphological and genetic composition, similar to that of the native β cells. iPS cell technology is a technique of transducing any cell types with key transcription factors to yield embryonic-like stem cells with high clonogenicity and is able to give rise into all cell lineages from three germ layers (endoderm, ectoderm, and mesoderm). This approach can generate β-like pancreatic cells that are fully functional as proven by either in vitro or in vivo studies. This novel proof-of-concept stem cell technology brings new expectations on applying stem cell therapy for diabetes mellitus in clinical settings.

Tissue Engineering Approaches to Cell-Based Type 1 Diabetes Therapy

“…A few studies have subjected iPSCs to directed differentiation protocols similar to those used with ESCs and successfully produced insulin + cells at similar percentages to that obtained for ESCs. 25,[32][33][34] Additionally, pancreatic precursor cells derived from murine or rhesus monkey iPSCs were found to reverse diabetes in immunodeficient mice after a month-long maturation period in vivo. 35,36 The safety of iPSCs, which typically are produced through adenoviral delivery systems that can activate known oncogenes, needs further investigation before clinical implementation can be pursued.…”

Cell-Based Therapy Approaches: The Hope for Incurable Diseases

“…ESCs and iPSCs can be induced to differentiate into IPCs [89], yet, the glucose-sensing and insulin-secreting abilities of the derived cells are disputed [91,92,96]. Moreover, ESC/iPSC-derived IPCs do not mature into functional β-cells in vitro [92] and their differentiation efficiency is low.…”

Diabetes mellitus and cellular replacement therapy: Expected clinical potential and perspectives

“…Now it is known that PSCs may be successfully derived from various human somatic cells, such as dermal fibroblasts and keratinocytes [26] . Therefore, autologous pancreatic islets may be differentiated from induced PSCs that derived from DM subjects using integrating retroviral vectors that integrate into the host genome and after then it may replace to donor [27][28][29] .…”

“…Overall, the results of the recent studies are controversial due to lack uniformity of design and protocols related techniques of the cell isolation and delivery methods [33] . Moreover, accordingly opinion Soejitno et al [26] , the implementation of the stem cell in the routine clinical setting is limited due to risk of malignancy, autoimmune response and rejection of the transplanted cells. Indeed, the allogeneic immune rejection of human ESC-derived cells is considered the main cause of efficacy limitation in recipients [23] .…”

“…However, there are advantages of therapeutic cloning affected the potential of cells originated from non-β-cell and related with avoiding of the autoimmune response after transplantation [44] . Despite there is a high similarity of different types of ESCs, effectiveness of reprogramming methods is low and successful result of stem cell culturing appears in 0.01%-0.1% cases [26] . These facts are considered a cause for design of stem cell bank in short-term perspective [45] .…”