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Table 1 Summary of the major MSC-derived studies in pre-clinical animal models of T1D

From: CRISPR-targeted genome editing of mesenchymal stem cell-derived therapies for type 1 diabetes: a path to clinical success?

Treatment type Intervention Outcomes Fresh/frozen Reference
Immunomodulation Mice received 1 × 106 AD-MSCs by i.p. injection Reversal of hyperglycaemia characterised by increased serum insulin, amylin, and GLP-1 levels. Downregulation of the CD4+ Th1-based immune response and expansion of Tregs in the pancreatic lymph nodes. Fresh [13]
Mice received 1 × 105 MSCs either i.p. or i.v. Reduced infiltration of T cells to pancreatic islets associated with preferential migration of MSCs to pancreatic lymph nodes. Fresh [14]
Mice received 0.5 × 106 MSCs administered systemically Reduced blood glucose levels and an increase in morphologically normal pancreatic islets. Fresh [16]
Rats received 2–4 × 106 MSCs via tail vein injection Enhanced insulin secretion and sustained normoglycaemia. Islets from treated rats co-expressed high levels of Pdx-1 and insulin. Fresh [17]
Mice received a co-transplantation of primary hBMSCs and human islets at serial ratios under the kidney capsule Good blood glucose control and increased levels of serum insulin and C-peptide when islets were co-transplanted with hBMSCs. hBMSCs also increased the percentage of Tregs and prevented cytokine-induced loss-of-function of transplanted islets. Fresh [19]
Mice received 5 × 105 MSCs injected i.v. once a week for 4 weeks BALB/c-MSC trafficked to the pancreatic lymph nodes of treated animals. Administration of BALB/c-MSC temporarily resulted in reversal of hyperglycaemia in 90% of treated animals. Fresh [30]
IPC differentiation Chemical differentiation BMSCs formed islet-like clusters containing IPCs that expressed multiple pancreatic genes. The clusters released insulin in a glucose-dependent manner and ameliorated diabetes in STZ-treated nude mice. Fresh [6]
Chemical differentiation BMSCs differentiated into IPCs and acquired islet-like architecture after transplantation, developed an endocrine gene expression profile and demonstrated glucose-responsive insulin secretion. Subcapsular renal transplantation of these aggregates lowered circulating blood glucose levels. Fresh [8]
Chemical differentiation Differentiated BMSCs expressed multiple pancreatic genes and exhibited glucose-responsive insulin secretion. Transplantation into STZ-diabetic mice imparted reversal of hyperglycaemia and an improved IPGTT. Fresh [9]
Chemical differentiation Differentiation cells expressed pancreatic genes and displayed glucose-responsive insulin secretion. Transplantation of differentiated cells into diabetic rats reduced blood sugar levels. Fresh [33]
Viral-mediated differentiation Differentiated cells expressed all four islet hormones and demonstrated glucose-responsive insulin secretion. Cell transplantation into STZ-diabetic immune-deficient mice resulted in further differentiation, including induction of NeuroD1 and reduction of hyperglycaemia. Fresh [11]
Viral-mediated differentiation hMSCs differentiated into IPCs that expressed multiple islet genes and released insulin/C-peptide in a weak glucose-responsive manner. Upon transplantation into STZ-diabetic mice, normoglycaemia was obtained within 2 weeks and maintained for at least 42 days. Fresh [12]
Viral-mediated differentiation Differentiated AD-MSC expressed some islet genes and secreted increasing amounts of insulin in response to increasing concentrations of glucose. Transplantation in STZ-diabetic rats resulted in lowered blood glucose and higher glucose tolerance. Fresh [36]
Viral-mediated differentiation Expression of Pdx1 in AD-MSCs did not induce the pancreatic phenotype in vitro. Upon transplantation, the cells engrafted in the pancreas, wherein they expressed insulin and C-peptide, significantly decreased blood glucose levels, and increased survival. Fresh [37]
Viral-mediated differentiation Body weight in diabetic mice that received GFP-mMSCs expressing the human insulin gene was increased by 6% within 6 weeks after treatment. Fresh [39]
  1. AD-MSC adipose-derived mesenchymal stem cell, BMSC bone marrow mesenchymal stem cell, CD cluster of differentiation, GFP green fluorescent protein, GLP-1 glucagon-like peptide 1, hBMSC human bone marrow mesenchymal stem cell, i.p. intraperitoneal, IPC insulin producing cell, IPGTT intraperitoneal glucose tolerance test, i.v. intravenous, MSC mesenchymal stem cell, Pdx-1 pancreatic and duodenal homeobox 1, STZ streptozotocin, T regs regulatory T cells, mMSC murine mesenchymal stem cell, BALB/c-MSC Bagg Albino mesencymal stem cells