Characteristics and clinical applications of Wharton’s jelly-derived mesenchymal stromal cells

Liau, Ling Ling; Ruszymah, B H I; Ng, Min Hwei; Law, Jia Xian

doi:10.1016/j.retram.2019.09.001

Cited by 90 publications

(83 citation statements)

References 100 publications

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“…This gelatinous substance contains primitive mesenchymal stem cells (MSC) [15] and yields the highest concentration of MSC per milliliter of other allogenic tissues [16]. Wharton's jelly MSC may be more effective than MSC from adult tissues in the treatment of several conditions, and though safe and efficacious, more studies are required to justify their routine use in the clinics [17]. Wharton's jelly also contains high amounts of extracellular matrix components, including collagen, hyaluronic acid, and sulfated proteoglycans [18].…”

Section: Introductionmentioning

confidence: 99%

Umbilical cord-derived Wharton’s jelly for regenerative medicine applications

Gupta

El-Amin²,

Levy

et al. 2020

J Orthop Surg Res

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Background: The last decade has seen an explosion in the interest in using biologics for regenerative medicine applications, including umbilical cord-derived Wharton's Jelly. There is insufficient literature assessing the amount of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes in these products. The present study reports the development of a novel Wharton's jelly formulation and evaluates the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes. Methods: Human umbilical cords were obtained from consenting caesarian section donors. The Wharton's jelly was then isolated from the procured umbilical cord and formulated into an injectable form. Randomly selected samples from different batches were analyzed for sterility testing and to quantify the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles. Results: All samples passed the sterility test. Growth factors including IGFBP 1, 2, 3, 4, and 6, TGF-α, and PDGF-AA were detected. Several immunomodulatory cytokines, such as RANTES, IL-6R, and IL-16, were also detected. Proinflammatory cytokines MCSFR, MIP-1a; anti-inflammatory cytokines TNF-RI, TNF-RII, and IL-1RA; and homeostatic cytokines TIMP-1 and TIMP-2 were observed. Cytokines associated with wound healing, ICAM-1, G-CSF, GDF-15, and regenerative properties, GH, were also expressed. High concentrations of hyaluronic acid were observed. Particles in the extracellular vesicle size range were also detected and were enclosed by the membrane, indicative of true extracellular vesicles. Conclusion: There are numerous growth factors, cytokines, hyaluronic acid, and extracellular vesicles present in the Wharton's jelly formulation analyzed. The amount of these factors in Wharton's jelly is higher compared with other biologics and may play a role in reducing inflammation and pain and augment healing of musculoskeletal injuries.

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Section: Introductionmentioning

confidence: 99%

Umbilical cord-derived Wharton’s jelly for regenerative medicine applications

Gupta

El-Amin²,

Levy

et al. 2020

J Orthop Surg Res

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“…Several kinds of stem cells have been utilized for this purpose; moreover, Wharton's jellyderived mesenchymal stem cells (WJMSCs) are considered to be one of the most promising cell sources of regeneration medicine due to their fewer ethical issues and safety concerns when compared to the tumorigenicity and ethical controversy of ESCs and the tumor formation and immunogenicity potential of iPSCs [6][7][8]. Further, WJMSCs isolated from fetal tissue have several unique beneficial properties including easy isolation, higher proliferation capacity, and potentially strong immunomodulatory effects [9]. Previous studies have reported the beneficial effects of WJMSCs on large full-thickness cutaneous wounds in animal models [10,11].…”

Section: Introductionmentioning

confidence: 99%

PF-127 hydrogel plus sodium ascorbyl phosphate improves Wharton’s jelly mesenchymal stem cell-mediated skin wound healing in mice

et al. 2020

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Background: Factors such as poor engraftment, retention, and survival of the transplanted stem cells are deemed to limit their therapeutic efficacy for wound regeneration. Hence, it is necessary to explore these issues in order to resolve them. In this study, we aim to investigate the role of Pluronic F-127 (PF-127) hydrogel plus antioxidant sodium ascorbyl phosphate (SAP) in enhancing Wharton's jelly mesenchymal stem cell (WJMSC)-mediated effectiveness on full-thickness skin wound healing in mice. Methods: First, the cytotoxicity of PF-127 and the biological effect of SAP on the survival of WJMSCs were tested in vitro using cell viability and proliferation assays. Next, a cell suspension containing WJMSCs, PF-127, and SAP was topically administered onto an 8-mm diameter excisional full-thickness wound bed. Eight days after transplantation, the mice were sacrificed and the skin tissue was excised for histological and immunohistochemical analysis. Finally, in vivo distribution of transplanted WJMSCs was traced to investigate cell engraftment and the potential therapeutic mechanism. Results: PF-127 was found to be cytotoxic to WJMSCs while SAP significantly improved the survival of PF-127embedded WJMSCs. When this combination was topically transplanted onto the wound bed, wound healing was facilitated and dermis regeneration was achieved on the 8th day after surgery, as evidenced by an increase in dermal thickness, newly developed hair follicles, and collagen fiber deposition accompanied by a reduction in scar width. Further, immunohistochemical analysis demonstrated a higher number of anti-inflammatory M2 macrophages, proliferating cells, and newly formed blood vessels in the WJMSCs/PF-127/SAP group relative to all other groups. In addition, in vivo tracking results revealed a highly enhanced engraftment of WJMSCs accumulated in the dermis in the WJMSCs/PF-127/SAP group. (Continued on next page)Conclusions: SAP significantly improves the survival of WJMSCs in PF-127 encapsulation. Further, PF-127 plus SAP is an effective combination that enhances WJMSC engraftment in the dermis, which then promotes full-thickness wound healing through potential M2 macrophage formation and angiogenesis.

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“…UC-MSCs were used for the treatment of SCI due to its ease of sourcing, excellent in vitro expansion capacity, fast proliferation and low immunogenicity. UC-MSCs have low expression of HLA-ABC and no expression of HLA-DR and co-stimulatory antigens such as CD40, CD80, and CD86 that are associated with immune rejection [ 33 , 55 ]. Additionally, UC-MSCs have more robust growth and more potent immune suppression property compared to BMSCs.…”

Section: Mesenchymal Stem Cell Therapy For Spinal Cord Injurymentioning

confidence: 99%

Treatment of spinal cord injury with mesenchymal stem cells

Liau

Looi²,

Chia³

et al. 2020

Cell Biosci

Self Cite

146

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Background Spinal cord injury (SCI) is the damage to the spinal cord that can lead to temporary or permanent loss of function due to injury to the nerve. The SCI patients are often associated with poor quality of life. Results This review discusses the current status of mesenchymal stem cell (MSC) therapy for SCI, criteria to considering for the application of MSC therapy and novel biological therapies that can be applied together with MSCs to enhance its efficacy. Bone marrow-derived MSCs (BMSCs), umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (ADSCs) have been trialed for the treatment of SCI. Application of MSCs may minimize secondary injury to the spinal cord and protect the neural elements that survived the initial mechanical insult by suppressing the inflammation. Additionally, MSCs have been shown to differentiate into neuron-like cells and stimulate neural stem cell proliferation to rebuild the damaged nerve tissue. Conclusion These characteristics are crucial for the restoration of spinal cord function upon SCI as damaged cord has limited regenerative capacity and it is also something that cannot be achieved by pharmacological and physiotherapy interventions. New biological therapies including stem cell secretome therapy, immunotherapy and scaffolds can be combined with MSC therapy to enhance its therapeutic effects.

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Characteristics and clinical applications of Wharton’s jelly-derived mesenchymal stromal cells

Cited by 90 publications

References 100 publications

Umbilical cord-derived Wharton’s jelly for regenerative medicine applications

Umbilical cord-derived Wharton’s jelly for regenerative medicine applications

PF-127 hydrogel plus sodium ascorbyl phosphate improves Wharton’s jelly mesenchymal stem cell-mediated skin wound healing in mice

Treatment of spinal cord injury with mesenchymal stem cells

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