Systematic review of the study of cell therapy on pancreatic marker expression for β-cell regeneration.

Type 1 diabetes mellitus (T1DM) is the most common chronic autoimmune disease in young patients [1]. It is considered an autoimmune disease as it results from the destruction of the insulin-producing β-cells of the pancreas by self-reactive immune cells. As a result, the body becomes insulin deficient and hyperglycemic[2]. Administration or injection of exogenous insulin is the most efficient current treatment at present, however, it cannot mimic the endogenous insulin secreted by a healthy pancreas. Consequently, alternative therapies have been sought to treat this disease. One of them is cell therapy. A registry prepared in 2017 compared the therapeutic potential of differentiated and undifferentiated mesenchymal stem cells as a new therapeutic line for T1DMD. The study was conducted in animals, 40 female albino rats were separated into four groups of 10 each. Group 1 was control, group II was the diabetic group, and group III and IV were injected with streptozotocin. Group III was transplanted with bone marrow-derived MSCs, and group IV with differentiated pluripotent insulin-producing cells. The results showed that the MSCs group reduced hyperglycemia in rats after 15 days, while group IV (IPSc) normalized glucose levels by day 7 [3]. In 2020 Shuai Chen et al. differentiated The pluripotent stem cells into β-like cells with some functional similarities to mature β cells through stepwise differentiation mimicking normal development. The obtained IPCs express specific biomarkers of normal β cells that identify a terminally differentiated state, such as NEUROD1 (downstream factor of NGN3 that is expressed in most pancreatic endocrine cells, including β cells) and PDX1 [2]. In a 2019 registry, adipose tissue-derived MSCs (ADMSCs) were particularly used, this thanks to the abundance and easy isolation of these cells. The potential therapeutic benefits of ADMSCs for the treatment of T1DMD are described. Adipose tissue-derived mesenchymal stromal cells (ADMSCs) were differentiated into IPCs in culture medium supplemented with exendin-4, pentagastrin, activin-A, beta-cellulin, nicotinamide, hepatocyte growth factor (HGF) and glucagon-like peptide-1 (GLP-1). As a result differentiated IPCs expressed some proteins, and transcription factors including Pdx-1 and Ngn3 [4]. In 2021, Khamis T et al. administered MSCs isolated from breast milk to a type 1 diabetic rat model. Overall, this study was designed to explore the potential therapeutic value of human MSCs isolated from human milk in type 1 Diabetes Mellitus. The authors demonstrated that the mRNA expression of pancreatic embryonic transcriptional factor (PDX1) was significantly increased (p < 0.001) compared to the control group [5]. In [6] different models and mechanisms of endocrine cell regeneration are proposed: β-cell proliferation, neogenesis and transdifferentiation. This cell regeneration evaluates new cell sources, such as iPSCs, MSCs and cord blood-derived stem cells. Differentiation of insulin-producing cells results from induced pluripotent cells. Expression of markers such as Pdx1 is mentioned as a consequence of embryonic cell differentiation. This differentiation involves β-cells involving active pathways, such as growth factors like activin and retinoic acid