Umbilical Cord Perivascular Cells Research Articles

Chromatographic Scalable Method to Isolate Engineered Extracellular Vesicles Derived from Mesenchymal Stem Cells for the Treatment of Liver Fibrosis in Mice.

New therapeutic options for liver cirrhosis are needed. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have emerged as a promising tool for delivering therapeutic factors in regenerative medicine. Our aim is to establish a new therapeutic tool that employs EVs derived from MSCs to deliver therapeutic factors for liver fibrosis. EVs were isolated from supernatants of adipose tissue MSCs, induced-pluripotent-stem-cell-derived MSCs, and umbilical cord perivascular cells (HUCPVC-EVs) by ion exchange chromatography (IEC). To produce engineered EVs, HUCPVCs were transduced with adenoviruses that code for insulin-like growth factor 1 (AdhIGF-I-HUCPVC-EVs) or green fluorescent protein. EVs were characterized by electron microscopy, flow cytometry, ELISA, and proteomic analysis. We evaluated EVs' antifibrotic effect in thioacetamide-induced liver fibrosis in mice and on hepatic stellate cells in vitro. We found that IEC-isolated HUCPVC-EVs have an analogous phenotype and antifibrotic activity to those isolated by ultracentrifugation. EVs derived from the three MSCs sources showed a similar phenotype and antifibrotic potential. EVs derived from AdhIGF-I-HUCPVC carried IGF-1 and showed a higher therapeutic effect in vitro and in vivo. Remarkably, proteomic analysis revealed that HUCPVC-EVs carry key proteins involved in their antifibrotic process. This scalable MSC-derived EV manufacturing strategy is a promising therapeutic tool for liver fibrosis.

Porcine Umbilical Cord Perivascular Cells for Preclinical Testing of Tissue-Engineered Heart Valves.

Many children born with congenital heart disease need a heart valve repair or replacement. Currently available repair materials and valve replacements are incapable of growth, repair, and adaptation, rendering them inadequate for growing children. Heart valve tissue engineering (HVTE) aims to develop living replacement valves that can meet these needs. Among numerous cell sources for in vitro HVTE, umbilical cord perivascular cells (UCPVCs) are particularly attractive because they are autologous, readily available, and have excellent regenerative capacity. As an essential step toward preclinical testing of heart valves engineered from UCPVCs, the goal of this study was to establish methods to isolate, expand, and promote extracellular matrix (ECM) synthesis by UCPVCs from pigs (porcine umbilical cord perivascular cells [pUCPVCs]), as a relevant preclinical model. We determined that Dulbecco's modified Eagle's medium with 20% fetal bovine serum supported isolation and substantial expansion of pUCPVCs, whereas media designed for human mesenchymal stromal cell (MSC) expansion did not. We further demonstrated the capacity of pUCPVCs to synthesize the main ECM components of heart valves (collagen type I, elastin, and glycosaminoglycans), with maximal collagen and elastin per-cell production occurring in serum-free culture conditions using StemMACS™ MSC Expansion Media. Altogether, these results establish protocols that enable the use of pUCPVCs as a viable cell source for preclinical testing of engineered heart valves. Impact statement This study establishes methods to successfully isolate, expand, and promote the synthesis of the main extracellular matrix components of heart valves (collagen type I, elastin, and glycosaminoglycans) by porcine umbilical cord perivascular cells (pUCPVCs). These protocols enable further evaluation of pUCPVCs as an autologous, readily available, and clinically relevant cell source for preclinical testing of pediatric tissue-engineered heart valves.

A better reception for islets

Transplantation Pancreatic islet transplantation can stabilize blood glucose concentrations in individuals with type 1 diabetes, but transplant function decreases over time. Forbes et al. investigated the supportive effects of cotransplanting islets and human umbilical cord perivascular mesenchymal stromal cells (HUCPVCs). HUCPVCs inhibited T cells, expressed proregenerative and immune-regulatory markers in vitro, and increased islet vascularization in vivo. Cotransplanting human islets and HUCPVCs under the kidney capsule or via the hepatic portal vein improved control of blood glucose in diabetic immunodeficient and immunocompetent mouse models for up to 16 weeks. Sci. Transl. Med. 12 , eaan5907 (2020).

Umbilical Cord Perivascular Cells: A Mesenchymal Cell Source for Treatment of Tendon Injuries

Objective: To model the healing that umbilical cord perivascular cells effect in equines, we have used human umbilical cord perivascular cells (HUCPVCs) to repair tendon damage in a collagenase tendon injury model in immune- compromised rats. Animals: 48 Nude rats (Crl:NIH-Foxn1 rnu ) of 200-250 g weight were used. Procedure: The Achilles tendon was exposed by blunt dissection and, using a 30G needle, 30 µl of either a mixture of cells (2 x10 5 ) and collagenase, or collagenase alone, was injected close to the musculotendinous junction in the direction of the osteotendinous junction. Results: Harvested tendons showed the presence of HUCPVCs at the site of injury, whose morphology changed from ovoid to elongated over the 30 post-injury experimental time period. Human genes for collagen type 1 and β-actin were expressed at all time points and there was also a significant increase in tendon tensile strength and stiffness by 30 days post-injury in the experimental group. Conclusion: HUCPVCs facilitated regeneration in our model through changes in collagen organization; cell shape and orientation; and increase in mechanical properties over those of the untreated controls. Clinical Relevance: Cell therapy has been shown to be effective in treating tendon injuries, especially in equines. We have recently isolated a mesenchymal cell population from equine umbilical cords that is analogous to a well-characterized HUCPVC population. Our results indicate that HUCPVCs are a putative cell source for treating tendon injuries; and this model could explain the benefits of using analogous cells in equines.

Introduction to Cellular Therapy

Cell therapy represents a new frontier in the development of therapeutics for stroke. Aside from physical rehabilitation, few options exist to enhance recovery from stroke. Prior studies in the 1990s provided precedence for considering a cellular approach to treat neurological disorders with the pioneering work on transplantation in Parkinson disease. These trials furnished preliminary evidence for a modest benefit in young patients with a neurodegenerative disorder who underwent neural transplantation. From those initial studies, pilot work emerged on the application of cellular replacement in Huntington disease and other neurological disorders. In an entirely different area of medicine, stem cell transplantation in oncology provided support for the idea that stem cells could be administered intravenously for a range of disorders including stroke. Over the past decade, investigators accordingly began showing that intravenously injected stem cells from the bone marrow and umbilical cord could promote recovery in animal stroke models. Thus began a new area of investigation in which adult stem cells from other sources, rather than the brain, could be tested for therapeutic applications in stroke. As transplantation studies have been growing, it has also now clearly been established that the adult brain undergoes neurogenesis. Elegant work from Lindvall and Parent and others have shown that …

Application of stem cells in bone repair

Bone has the ability to repair minor injuries through remodeling. However, when the host source of osteoprogenitors is compromised at the defect site, one effective treatment may be cell-based therapy, as it replenishes the area of bone loss with cells possessing osteogenic potential. This review is a concise comparison of different types of stem cells that have the potential to be used in tissue-engineered scaffolds for bone repair. The clinical use of mesenchymal stem or stromal cells isolated from the bone marrow for treating various diseases has been well documented. However, the scarcity of these cells prompts the search for alternative sources of multipotential cells such as amniotic fluid stem cells and umbilical cord perivascular cells. Embryonic stem cells are another controversial source of cells with osteogenic potential. These cells have the ability to differentiate into all cell types of the adult body. Issues such as the use of human embryos and the risk of contamination from animal-derived culture components continue to prevent the therapeutic use of ESCs. As a result, abundant research has been carried out to design defined culture conditions for culturing ESCs, and alternative strategies such as the generation of induced pluripotent stem cells are being developed to eliminate the need for using embryos for cell derivation. In addition to the cell source, the ability to control stem cell differentiation into functional bone and the choice of biomaterial are also paramount objectives that are being examined in research and clinical trials.