Human Multipotent Stromal Cell Secreted Effectors Accelerate Islet Regeneration

Miljan Kuljanin et al., STEM CELLS

Cell-based therapies using human multipotent stromal cells (hMSC) to dampen autoimmunity while inducing islet regeneration represents a promising approach to treat diabetes. However, poor survival and retention of transplanted hMSC in the damaged pancreas complicates clinical translation. The research demonstrated that hMSC secrete an array of islet-regenerative proteins and intrapancreatic delivery of hMSC-conditioned media (CM) could stimulate islet regeneration without the need for cell transfer. Wnt-pathway stimulated hMSC CM-injection set in motion a cascade of events consistent with the emergence of functional islets. Discovery of hMSC-secreted, islet-regenerative effectors may lead to the development of cell-free therapies to combat diabetes.

Concise Review: Therapeutic Potential of the Mesenchymal Stem Cell Derived Secretome and Extracellular Vesicles for Radiation-Induced Lung Injury: Progress and Hypotheses

Siguang Xu et al., STEM CELLS Translational Medicine

Although it has been reported that soluble cytokines based on mesenchymal stem cells (MSCs) therapy that could attenuate radiation-induced lung injury (RILI), the mechanism of MSC-based secretome therapy for RILI is still not fully understood. This review summarized the recent progress regarding the potential mechanisms of MSCs therapy for RILI, with an emphasis on MSC-secreted cytokines and miRNAs as a safe and, effective cell-free therapy, which may be helpful to accelerate the strategy from bench to bedside.

Endothelial Differentiation G Protein-Coupled Receptor 5 Plays an Important Role in Induction and Maintenance of Pluripotency

Irina Neganova et al., STEM CELLS

Using a high-throughput RNA interference screen, authors identified 22 effectors of somatic cell-induced reprogramming, six of which belong to the G protein-coupled receptor (GPCR) family. The present study describes a new role for the GPCR family member, endothelial differentiation GPCR5 (EDG5; sphingosine-1-phosphate receptor 2), whose downregulation in human embryonic stem cells (hESCs) or during the initiation period of reprogramming leads to abrogation of the pluripotent stem cell colony formation because of the defects in cytoskeleton organization and focal adhesions. Together, the data provide for the first time substantive evidence for EDG5 as a critical GPCR for the maintenance of pluripotency in hESC and successful reprogramming of human fibroblasts to human-induced pluripotent stem cells.

Mesenchymal Stem Cells and Induced Bone Marrow-Derived Macrophages Synergistically Improve Liver Fibrosis in Mice

Yusuke Watanabe et al., STEM CELLS Translational Medicine

Cirrhosis is a life-threatening condition. Thus, the development of novel therapeutic approaches for liver fibrosis regression and regeneration is urgently needed. The authors focused on two cell types; that is, bone marrow-derived mesenchymal stem cells (MSCs) and colony-stimulating factor-1-induced bone marrow-derived macrophages (id-BMMs), previously reported to be effective for cirrhosis, and showed that combination therapy with the two cell types synergistically improves liver function and fibrosis (over monotherapy with MSCs or id-BMMs), in part by enhancing host endogenous regenerative responses. The authors also, for the first time, succeeded in tracing the detailed behavior of administered cells in the liver by intravital imaging technology and believe that these studies pave the way for new treatments.