Transplantation of Human Menstrual Blood Progenitor Cells Improves Hyperglycemia by Promoting Endogenous Progenitor Differentiation in Type 1 Diabetic Mice

Abstract

Recently, a unique population of progenitor cells was isolated from human menstrual blood. The human menstrual blood progenitor cells (MBPCs) possess many advantages, such as the noninvasive acquisition procedure, broad multipotency, a higher proliferative rate, and low immunogenicity, and have attracted extensive attention in regenerative medicine. Preclinical studies to test the safety and efficacy of MBPCs have been underway in several animal models. However, relevant studies in type 1 diabetes mellitus (T1DM) have not yet been proceeded. Herein, we studied the therapeutic effect of MBPCs and the mechanism of b-cell regeneration after MBPC transplantation in the T1DM model. Intravenous injection of MBPCs can reverse hyperglycemia and weight loss, prolong lifespan, and increase insulin production in diabetic mice. Histological and immunohistochemistry analyses indicated that T1DM mice with MBPC transplantation recovered islet structures and increased the b-cell number. We further analyzed in vivo distribution of MBPCs and discovered that a majority of MBPCs migrated into damaged pancreas and located at the islet, duct, and exocrine tissue. MBPCs did not differentiate into insulin-producing cells, but enhanced neurogenin3 (ngn3) expression, which represented endocrine progenitors that were activated. Ngn3+ cells were not only in the ductal epithelium, but also in the islet and exocrine tissue. We analyzed a series of genes associated with the embryonic mode of b-cell development by real-time polymerase chain reaction and the results showed that the levels of those gene expressions all increased after cell transplantation. According to the results, we concluded that MBPCs stimulated b-cell regeneration through promoting differentiation of endogenous progenitor cells.

Human endometrial mesenchymal stem cells exhibit intrinsic anti-tumor properties on human epithelial ovarian cancer cells

“…MSCs have been shown the tropic properties towards damaged tissues38 and tumor microenvironment39, which improve the efficiency and target ability of MSC-based therapy. We and other groups have reported the potential application of EnSCs to restore function of injured tissues91238.…”

“…We and other groups have reported the potential application of EnSCs to restore function of injured tissues91238. However, there are some concerns about the potential risk of MSCs.…”

“…The human EnSCs were isolated from menstrual blood of a 40-year-old Chinese woman according to the protocol previously reported938 with approval from the institutional ethics committee and written informed consent was obtained. EnSCs were cultured in Chang Medium (S-Evans Biosciences, Hangzhou, China) with 5% CO 2 at 37 °C and were passaged every 4–6 days.…”

Endometrial stem cells repair injured endometrium and induce angiogenesis via AKT and ERK pathways

“…MenSCs were isolated and provided by the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University (Mou et al 2013, Wu et al 2014, Lai et al 2015. Briefly, human menstrual blood was collected The χ 2 test was applied.…”

Exosomes derived from human menstrual blood-derived stem cells alleviate fulminant hepatic failure

“…MenSCs exhibit higher proliferation rates than bone marrow-derived MSCs and can be easily obtained without invasive procedures [9–11]. In particular, our and other groups have reported that MenSCs induce low-level immunogenicity in clinical studies and can be expanded through at least 20 passages without genetic abnormalities [9, 12, 13]. The therapeutic potential of MenSCs has been demonstrated in several disease models, such as Duchenne muscular dystrophy, stroke, type 1 diabetes, premature ovarian failure, and myocardial infarction.…”