Regenerative Potential of the Product “CardioCell” Derived from the Wharton’s Jelly Mesenchymal Stem Cells for Treating Hindlimb Ischemia

Abstract

In recent years, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality in regenerative medicine. They hold great promise for treating civilization-wide diseases, including cardiovascular diseases, such as acute myocardial infarction and critical limb ischemia. MSCs isolated from Wharton’s jelly (WJ-MSCs) may be utilized in both cell-based therapy and vascular graft engineering to restore vascular function, thereby providing therapeutic benefits for patients. The efficacy of WJ-MSCs lies in their multipotent differentiation ability toward vascular smooth muscle cells, endothelial cells and other cell types, as well as their capacity to secrete various trophic factors, which are potent in promoting angiogenesis, inhibiting apoptosis and modulating immunoreaction. Ischemic limb disease is caused by insufficient nutrient and oxygen supplies resulting from damaged peripheral arteries. The lack of nutrients and oxygen causes severe tissue damage in the limb, thereby resulting in severe morbidities and mortality. The therapeutic effects of the conventional treatments are still not sufficient. Cell transplantations in small animal model (mice) are vital for deciphering the mechanisms of MSCs’ action in muscle regeneration. The stimulation of angiogenesis is a promising strategy for the treatment of ischemic limbs, restoring blood supply for the ischemic region. In the present study, we focus on the therapeutic properties of the human WJ-MSCs derived product, Cardio. We investigated the role of CardioCell in promoting angiogenesis and relieving hindlimb ischemia. Our results confirm the healing effect of CardioCell and strongly support the use of the WJ-MSCs in regenerative medicine.

The Importance of HLA Assessment in “Off-the-Shelf” Allogeneic Mesenchymal Stem Cells Based-Therapies

“…Although, the project is still in progress, the results seem to point out to the “CardioCell” as a possible alternative in the treatment of cardiovascular diseases. Our in vitro and in vivo studies have shown so far, that WJ-MSCs possess high regenerative potential and most importantly they are safe for recipients [72,113]. Our initial clinical results suggest that the level of donor specific antibodies (DSAs) in patients does not change even after multiple administrations, which might indicate that immunization does not occur (unpublished data).…”

“…The number of factors released by MSCs is remarkable. For example, secretion of proangiogenic factors such as vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and transforming growth factor-β1 (TGF-β1) is able to enhance in vivo angiogenesis through the increase of microvascular density thus promoting blood flow recovery in the ischemic tissue [27,71,72].…”

Wharton’s jelly mesenchymal stem cells embedded in PF-127 hydrogel plus sodium ascorbyl phosphate combination promote diabetic wound healing in type 2 diabetic rat

“…Accumulating evidences have pointed out that MSCs stimulates wound healing by promoting angiogenesis by releasing angiogenic cytokines in diabetic ulcer [ 55 , 56 ]. WJMSCs not only show multipotent differentiation toward angiogenic cell, such as vascular smooth muscle cells, endothelial cells, and other cell types, but also can secrete a variety of regulatory factors to promoting angiogenesis, inhibiting apoptosis, and modulating immunoreaction [ 57 ]. In our study, more CD31-positive cells were detected in the WJMSCs + PF-127 + 400 μM SAP group compared to other groups, demonstrating that the transplantation of WJMSCs encapsulated with PF-127 and SAP improved the angiogenesis in the diabetic wound.…”

“Bridging the Gap” Everything that Could Have Been Avoided If We Had Applied Gender Medicine, Pharmacogenetics and Personalized Medicine in the Gender-Omics and Sex-Omics Era

“…Interestingly, during the first few hours after AMI, complex local healing processes and inflammatory reactions are crucial in determining the risk of wall remodelling. Soluble molecules, resident and circulating cells and micro-RNAs finely mediate inflammation and regenerative progression by determining the fate of the heart after the infarction [71][72][73][74]. Basically, imbalance in any healing process and unrestrained ECM proteolysis cause a delayed remedy, while lasting chronic lesions in any district may affect the normal organ/tissue functions with consequent failure and malfunction [75][76][77].…”