Autologous Pluripotent Stem Cell–Derived β-Like Cells for Diabetes Cellular Therapy

Abstract

Development of stem cell technologies for cell replacement therapy has progressed rapidly in recent years. Diabetes has long been seen as one of the first applications for stem cell-derived cells because of the loss of only a single cell type-the insulin-producing β-cell. Recent reports have detailed strategies that overcome prior hurdles to generate functional β-like cells from human pluripotent stem cells in vitro, including from human induced pluripotent stem cells (hiPSCs). Even with this accomplishment, addressing immunological barriers to transplantation remains a major challenge for the field. The development of clinically relevant hiPSC derivation methods from patients and demonstration that these cells can be differentiated into β-like cells presents a new opportunity to treat diabetes without immunosuppression or immunoprotective encapsulation or with only targeted protection from autoimmunity. This review focuses on the current status in generating and transplanting autologous β-cells for diabetes cell therapy, highlighting the unique advantages and challenges of this approach.

Biomaterials for Personalized Cell Therapy

“…[115] Some strategies for differentiating iPSCs toward patient-specific therapeutic cells are under development but these cells may still require protection from the immune system. [98,116] To protect and support cells, important material design criteria include pore size, material dimensions, and oxygen sources. [117] Additionally, precision biomaterials can be designed to incorporate bioactive components to improve cell functionality, [118] promote host vascularization for increased oxygen supply, [119,173] and modulate the host immune system.…”

Pancreatic β-cell regeneration: advances in understanding the genes and signaling pathways involved

“…Great progress has been made in the field of in vitro differentiation of human embryonic and induced pluripotent stem cells toward insulin-producing cells, including the generation of stem cell-derived β cells from patients with T1D, leading to an ongoing clinical trial to assess their safety in humans [2]. Recent advances in studies with animal models are also beginning to provide compelling evidence to suggest in vivo β-cell regeneration as a viable alternative future approach to restoring β-cell mass in diabetic patients.…”

Hydrogel platform for in vitro three-dimensional assembly of human stem cell-derived β cells and endothelial cells

“…Currently a major challenge in the field of diabetes cell replacement therapy is sourcing of sufficient numbers of glucose-responsive insulin-secreting β cells [18]. Differentiated hESCs offer a potentially unlimited number of cells for this purpose [19], and this approach is enhanced by improving the maturation of the generated SC-β cells [20]. The inclusion of endothelial cells with SC-β cells could be combined with macroporous scaffolds that enable retrievability [16,21] or other beneficial materials [22][23][24][25][26] to develop a more comprehensive transplantation strategy for diabetes.…”