Abstract
Cell therapy using renal progenitors differentiated from human embryonic stem cells (hESCs) or induced pluripotent stem cells (hiPSCs) has the potential to significantly reduce the number of patients receiving dialysis therapy. However, the differentiation cultures may contain undifferentiated or undesired cell types that cause unwanted side effects, such as neoplastic formation, when transplanted into a body. Moreover, the hESCs/iPSCs are often genetically modified in order to isolate the derived renal progenitors, hampering clinical applications. To establish an isolation method for renal progenitors induced from hESCs/iPSCs without genetic modifications, we screened antibodies against cell surface markers. We identified the combination of four markers, CD9−CD140a+CD140b+CD271+, which could enrich OSR1+SIX2+ renal progenitors. Furthermore, these isolated cells ameliorated renal injury in an acute kidney injury (AKI) mouse model when used for cell therapy. These cells could contribute to the development of hiPSC-based cell therapy and disease modeling against kidney diseases.
Highlights
Cell therapy using renal progenitors differentiated from human embryonic stem cells or induced pluripotent stem cells has the potential to significantly reduce the number of patients receiving dialysis therapy
We previously showed that OSR1+SIX2+ cells differentiated from hiPSCs by our differentiation method contributed to renal lineage cells and mainly formed 3D proximal renal tubule-like structures, but not glomeruli-like structures, in vitro[15]
We identified the combination of CD9−CD140a+CD140b+CD271+ as most efficient for enriching renal progenitors derived from hiPSCs
Summary
Cell therapy using renal progenitors differentiated from human embryonic stem cells (hESCs) or induced pluripotent stem cells (hiPSCs) has the potential to significantly reduce the number of patients receiving dialysis therapy. To establish an isolation method for renal progenitors induced from hESCs/iPSCs without genetic modifications, we screened antibodies against cell surface markers. We identified the combination of four markers, CD9−CD140a+CD140b+CD271+, which could enrich OSR1+SIX2+ renal progenitors. These isolated cells ameliorated renal injury in an acute kidney injury (AKI) mouse model when used for cell therapy. In order to solve these problems, regenerative medicine strategies using embryonic renal progenitors differentiated from human embryonic stem cells (hESCs) or induced pluripotent stem cells (hiPSCs) have attracted attention
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