Trans-differentiation of mouse mesenchymal stem cells into pancreatic β-like cells by a traditional anti-diabetic medicinal herb Medicago sativa L

J Tradit Complement Med. 2022 Feb 21;12(5):466-476. doi: 10.1016/j.jtcme.2022.02.002. eCollection 2022 Sep.

Abstract

Background and aim: Medicago sativa L. is a medicinal herb first cultivated in ancient Iran. Traditionally, it has been utilized for the treatment of several disorders. The plant has been in the human diet for at least 1500 years. Although the hypoglycaemic and anti-diabetic effects of the plant have been approved in traditional medicine, further investigations are needed to support the rational use of M. sativa by humans. This project aimed to evaluate the trans-differentiation potential of bone marrow mesenchymal stem cells (MSCs) to pancreatic β-like cells (insulin-producing cells; IPCs) under the influence of M. sativa extract.

Experimental procedure: Bone marrow MSCs isolated, characterized, and then treated by flower or leaf extract of M. sativa. Beta-cell characteristics of the differentiated cells were evaluated by several techniques, including specific staining, QPCR, immunofluorescence, and ELISA.

Results: The results showed that the differentiated cells were able to express some specific pancreatic genes (PDX-1, insulin1, and insulin2) and proteins (insulin receptor beta, insulin, proinsulin, and C peptide). Furthermore, ELISA analysis indicated the ability of these cells in the production and secretion of insulin, after exposure to glucose.

Conclusion: Overall, both the flower and leaf extract of M. sativa had the potential of differentiation induction of MSCs into IPCs with the characteristics of pancreatic β-like cells. Therefore, M. sativa, as an herbal drug, may be beneficial for the treatment of diseases including diabetes.

Keywords: Medicago sativa L.; Medicinal herbs; Mesenchymal stem cells; Pancreatic β-cells; Trans-differentiation.