Stem Cells and Regenerative Medicine: Myth or Reality of the 21th Century

Abstract

Since the 1960s and the therapeutic use of hematopoietic stem cells of bone marrow origin, there has been an increasing interest in the study of undifferentiated progenitors that have the ability to proliferate and differentiate into various tissues. Stem cells (SC) with different potency can be isolated and characterised. Despite the promise of embryonic stem cells, in many cases, adult or even fetal stem cells provide a more interesting approach for clinical applications. It is undeniable that mesenchymal stem cells (MSC) from bone marrow, adipose tissue, or Wharton's Jelly are of potential interest for clinical applications in regenerative medicine because they are easily available without ethical problems for their uses. During the last 10 years, these multipotent cells have generated considerable interest and have particularly been shown to escape to allogeneic immune response and be capable of immunomodulatory activity. These properties may be of a great interest for regenerative medicine. Different clinical applications are under study (cardiac insufficiency, atherosclerosis, stroke, bone and cartilage deterioration, diabetes, urology, liver, ophthalmology, and organ's reconstruction). This review focuses mainly on tissue and organ regeneration using SC and in particular MSC.

hucMSC Exosome-Derived GPX1 Is Required for the Recovery of Hepatic Oxidant Injury

“…Specifically, 8 mg/kg hucMSC-Ex failed to rescue recipient animals from liver failure, but 60% and 90% of mice recovered from 16 and 32 mg/kg of hucMSC-Ex treatment, respectively ( Figure 1D). Also, serum ALT (alanine aminotransferase) and AST (aspartate aminotransferase) decreased in animals given 8 mg/kg hucMSC-Ex at 72 hr post-injection, confirming that hucMSC-Ex reduced acute extensive liver injury by CCl 4 (Figures 1E and 1F; n = 5; *p < 0.05, **p < 0.01, ***p < 0.001).…”

“…CCl 4 and H 2 O 2 are model hepatotoxicants. 32,40 They were used to develop a mouse liver injury model and study the antioxidant effects of hucMSC-Ex.…”

“…To assess the therapeutic potential of hucMSC-Ex, 8,16, and 32 mg/kg (tail vein or oral gavage) was given 24 hr after the administration of CCl 4 . For the tail vein administration of hucMSC-Ex, all animals infused with 8 mg/kg died of liver failure, and half survived after treatment with 16 mg/kg.…”

“…Human umbilical cord is a transplantable source of MSCs and human umbilical cord-derived MSCs (hucMSCs) are of interest in regenerative medicine for liver injury because of low cost, minimal invasiveness, convenient isolation, low immunogenicity and immunomodulatory activity, and differentiation multipotency. [2][3][4] Results from phase I and II clinical studies of hucMSC transplantation for patients with decompensated liver cirrhosis showed that hucMSCs may improve liver function and clinical symptoms (https://ClinicalTrials.gov identifier NCT0134225).…”

“…Antioxidant and anti-apoptotic effects of hucMSCs-Ex on CCl 4 -and H 2 O 2 -induced hepatic injury in vitro and in vivo were also investigated, and hucMSC-Ex-derived GPX1 promoted detoxification of CCl 4 and H 2 O 2 and inhibited oxidative stress and apoptosis in vitro and in vivo. Our results provide a better understanding for using hucMSC-Ex for treating liver injury.…”