An overview on small molecule-induced differentiation of mesenchymal stem cells into beta cells for diabetic therapy

Abstract

The field of regenerative medicine provides enormous opportunities for generating beta cells from different stem cell sources for cellular therapy. Even though insulin-secreting cells can be generated from a variety of stem cell types like pluripotent stem cells and embryonic stem cells, the ideal functional cells should be generated from patients' own cells and expanded to considerable levels by non-integrative culture techniques. In terms of the ease of isolation, plasticity, and clinical translation to generate autologous cells, mesenchymal stem cell stands superior. Furthermore, small molecules offer a great advantage in terms of generating functional beta cells from stem cells. Research suggests that most of the mesenchymal stem cell-based protocols to generate pancreatic beta cells have small molecules in their cocktail. However, most of the protocols generate cells that mimic the characteristics of human beta cells, thereby generating "beta cell-like cells" as opposed to mature beta cells. Diabetic therapy becomes feasible only when there are robust, functional, and safe cells for replacing the damaged or lost beta cells. In this review, we discuss the current protocols used to generate beta cells from mesenchymal cells, with emphasis on small molecule-mediated conversion into insulin-producing beta cell-like cells. Our data and the data presented from the references within this review would suggest that although mesenchymal stem cells are an attractive cell type for cell therapy they are not readily converted into functional mature beta cells.

Alginate/Pluronic F127-based encapsulation supports viability and functionality of human dental pulp stem cell-derived insulin-producing cells

“…In MSC-based protocols, two main step IPC differentiation were involved. The initial stage, MSCs were induced into pancreatic progenitor followed by βcell maturation [45]. However, three-stage differentiation protocol was involved in this study.…”

Therapeutic Potential of Wharton’s Jelly Mesenchymal Stem Cells for Diabetes: Achievements and Challenges

“…In addition to immunomodulatory functions and paracrine signaling, the differentiation potential of WJ-MSCs down several lineages adds a lot to their therapeutic potential, not only for DM, but also for a wide array of other diseases (Can et al, 2017). In fact, several pre-clinical studies reported the differentiation potential of WJ-MSCs into insulin producing cells (IPCs) using various induction protocols, and inducing extrinsic factors (Kassem et al, 2016;Pavathuparambil Abdul Manaph et al, 2019).…”

“…But still on the other hand, several elegant studies and review articles attempt to investigate the differentiation potential of MSCs into various lineages other than mesoderm (Urrutia et al, 2019). Insulin producing cells is definitely one of these lineages (Enderami et al, 2018;Päth et al, 2019;Pavathuparambil Abdul Manaph et al, 2019). Accordingly, we recommend that interested scientists should also consider developing novel strategies and enhancing induction protocols to generate IPCs from these WJ-MSCs.…”

Mesenchymal Stem Cells as a Promising Cell Source for Integration in Novel In Vitro Models

“…Recent studies have further highlighted MSCs’ rich potential as a cell source in revealing these cells’ capacity to differentiate not only into the “classic” MSC cell lineages reported in dozens of studies (e.g., chondrocytes, osteoblasts and adipocytes) [ 9 , 25 , 26 , 27 ] but also into additional cell types, including the following ( Figure 2 )—hepatocytes [ 28 , 29 , 30 ] ( Figure 2 A), cardiomyocytes [ 31 , 32 , 33 , 34 ] ( Figure 2 B), neurons [ 35 , 36 , 37 , 38 ] ( Figure 2 C), epithelium [ 39 , 40 ] ( Figure 2 D), endothelial cells [ 41 , 42 , 43 ] ( Figure 2 E), pancreatic β cells [ 44 , 45 , 46 ] ( Figure 2 F) and epidermis [ 47 , 48 , 49 ] ( Figure 2 G). It remains a challenge to develop methods that elicit MSC differentiation into other cell types such as gut, lung and microglial cells.…”