Systemic Administration of Multipotent Mesenchymal Stromal Cells Reverts Hyperglycemia and Prevents Nephropathy in Type 1 Diabetic Mice

Abstract

Multipotent mesenchymal stromal cells (MSCs), often labeled mesenchymal stem cells, contribute to tissue regeneration in injured bone and cartilage, as well as in the infarcted heart, brain, and kidney. We hypothesize that MSCs might also contribute to pancreas and kidney regeneration in diabetic individuals. Therefore, in streptozotocin (STZ)-induced type 1 diabetes C57BL/6 mice, we tested whether a single intravenous dose of MSCs led to recovery of pancreatic and renal function and structure. When hyperglycemia, glycosuria, massive beta-pancreatic islets destruction, and mild albuminuria were evident (but still without renal histopathologic changes), mice were randomly separated in 2 groups: 1 received 0.5 x 10(6) MSCs that have been ex vivo expanded (and characterized according to their mesenchymal differentiation potential), and the other group received the vehicle. Within a week, only MSC-treated diabetic mice exhibited significant reduction in their blood glucose levels, reaching nearly euglycemic values a month later. Reversion of hyperglycemia and glycosuria remained for 2 months at least. An increase in morphologically normal beta-pancreatic islets was observed only in MSC-treated diabetic mice. Furthermore, in those animals albuminuria was reduced and glomeruli were histologically normal. On the other side, untreated diabetic mice presented glomerular hyalinosis and mesangial expansion. Thus, MSC administration resulted in beta-pancreatic islets regeneration and prevented renal damage in diabetic animals. Our preclinical results suggest bone marrow-derived MSC transplantation as a cell therapy strategy to treat type 1 diabetes and prevent diabetic nephropathy, its main complication.

Bone Marrow-Derived Mesenchymal Stem cells Infusion Ameliorates Hyperglycemia, Dyslipidemia, Liver and Kidney Functions in Diabetic Rats

“…While hess et al [51] reported marked reduction of serum glucose occur as early as 4 days after transplantation of bone marrow derived cells into STZtreated mice due to stimulation of endogenous cells to proliferate and produce insulin. In accordance with our study, some evidences reported that single infusion of MSCs decrease blood glucose in STZ diabetic rats [52], [53]. Dong et al [52] reported that MSCs homed to pancreas of recipient rats and transdifferentiated into insulin-producing cells.…”

Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus

“…Although their immunomodulatory properties are not yet completely understood, their low immunogenic potential, together with their effects on immune responses, make them a promising therapeutic tool for severe refractory autoimmune diseases. MSCs have already been used in clinical trials as a treatment for acute graft-versus-host disease following allogeneic HSCT (25,26) and for autoimmune diseases such as systemic sclerosis (27) and type 1 diabetes mellitus (28).…”

Adipose mesenchymal stromal cells minimize and repair radiation-induced oral mucositis

“…MSCs have been applied for the repair of arthritis [63], cardiac muscle [152,153], lung tissue [150], diabetes [154], skin [81,83,155,156], skeletal tissue [157], and digestive tract tissue [87,148,158]. …”