Evaluation of Potential Application of Wharton’s Jelly-Derived Human Mesenchymal Stromal Cells and its Conditioned Media for Dermal Regeneration using Rat Wound Healing Model

2021 ◽  
pp. 1-14
Author(s):  
Caroline Mathen ◽  
Mrunal Ghag Sawant ◽  
Raghubansh Gupta ◽  
Wilfrid Dsouza ◽  
Shilpa G. Krishna
Keyword(s):  
Wound Healing ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Wound Care ◽  
Free Cell ◽  
Conditioned Media ◽  
Human Umbilical Cord ◽  
Human Mscs ◽  
Wound Model

Mesenchymal stromal cells and the derived conditioned media represent an area of tremendous medical interest and, among other clinical applications, are currently being extensively explored for wound healing. The aim of this study was to comparatively evaluate the wound healing potential of xeno-free human umbilical cord-derived mesenchymal stromal cells (MSCs) and the conditioned media (CM) in a full-thickness excision wound model in rats. The evaluation parameters included rate of wound healing, serum cytokine analyses, collagen content, histopathology, and hyperspectral imaging as an independent qualitative and quantitative tool. Both the cell-based and cell-free approaches scored better in lower inflammation, as evidenced in lower IL-10 and stable IL-6 levels, and improved rate of wound healing (<i>p</i> &#x3c; 0.0001). More importantly, no adverse reaction or rejection was observed although human MSCs and CM were used in a xenogeneic model. The presence of hFGF, hHGF, hGCSF, hIL-1Ra, hVEGF, and hIL-6 in the secretome may elucidate the regenerative potential of the xeno-free cell-based and cell-free approaches which have translational value for advanced wound care. The results revealed the therapeutic potential of both the cell-based and cell-free approaches for wound healing.

scholarly journals High Harvest Yield, High Expansion, and Phenotype Stability of CD146 Mesenchymal Stromal Cells from Whole Primitive Human Umbilical Cord Tissue

2009 ◽  
Vol 2009 ◽  
pp. 1-11 ◽  
Author(s):  
Rebecca C. Schugar ◽  
Steven M. Chirieleison ◽  
Kristin E. Wescoe ◽  
Benjamin T. Schmidt ◽  
Yuko Askew ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Human Mscs ◽  
Isolation And Purification ◽  
Cell Counts ◽  
Culturing Conditions

Human umbilical cord blood is an excellent primitive source of noncontroversial stem cells for treatment of hematologic disorders; meanwhile, new stem cell candidates in the umbilical cord (UC) tissue could provide therapeutic cells for nonhematologic disorders. We show novel in situ characterization to identify and localize a panel of some markers expressed by mesenchymal stromal cells (MSCs; CD44, CD105, CD73, CD90) and CD146 in the UC. We describe enzymatic isolation and purification methods of different UC cell populations that do not require manual separation of the vessels and stroma of the coiled, helical-like UC tissue. Unique quantitation of in situ cell frequency and stromal cell counts upon harvest illustrate the potential to obtain high numerical yields with these methods. UC stromal cells can differentiate to the osteogenic and chondrogenic lineages and, under specific culturing conditions, they exhibit high expandability with unique long-term stability of their phenotype. The remarkable stability of the phenotype represents a novel finding for human MSCs, from any source, and supports the use of these cells as highly accessible stromal cells for both basic studies and potentially therapeutic applications such as allogeneic clinical use for musculoskeletal disorders.

Mesenchymal stromal cells of human umbilical cord Wharton's jelly accelerate wound healing by paracrine mechanisms

Cytotherapy ◽  
2012 ◽  
Vol 14 (10) ◽  
pp. 1171-1181 ◽  
Author(s):  
Ryutaro Shohara ◽  
Akihito Yamamoto ◽  
Sachiko Takikawa ◽  
Akira Iwase ◽  
Hideharu Hibi ◽  
...  
Keyword(s):  
Wound Healing ◽  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Wharton’S Jelly ◽  
Human Umbilical Cord ◽  
Accelerate Wound Healing ◽  
Wharton's Jelly

Wound-healing potential of human umbilical cord blood–derived mesenchymal stromal cells in vitro—a pilot study

Cytotherapy ◽  
2015 ◽  
Vol 17 (11) ◽  
pp. 1506-1513 ◽  
Author(s):  
Hi-Jin You ◽  
Sik Namgoong ◽  
Seung-Kyu Han ◽  
Seong-Ho Jeong ◽  
Eun-Sang Dhong ◽  
...  
Keyword(s):  
Wound Healing ◽  
Pilot Study ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Umbilical Cord Blood ◽  
Stromal Cells ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord

scholarly journals Overexpression of IL-10 Enhances the Efficacy of Human Umbilical-Cord-Derived Mesenchymal Stromal Cells in E. coli Pneumosepsis

2019 ◽  
Vol 8 (6) ◽  
pp. 847 ◽  
Author(s):  
Mirjana Jerkic ◽  
Claire Masterson ◽  
Lindsay Ormesher ◽  
Stéphane Gagnon ◽  
Sakshi Goyal ◽  
...  
Keyword(s):  
Lung Injury ◽  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Injury Severity ◽  
Therapeutic Potential ◽  
Human Macrophage ◽  
Human Umbilical Cord ◽  
Macrophage Function ◽  
E Coli

Enhancing the immunomodulatory effects of mesenchymal stromal cells (MSCs) may increase their effects in sepsis. We tested the potential for overexpression of Interleukin-10 (IL-10) in human umbilical cord (UC) MSCs to increase MSC efficacy in Escherichia coli (E. coli) pneumosepsis and to enhance human macrophage function. Pneumonia was induced in rats by intratracheal instillation of E. coli ((2.0–3.0) × 109 Colony forming units (CFU)/kg). One hour later, animals were randomized to receive (a) vehicle; (b) naïve UC-MSCs; or (c) IL-10 overexpressing UC-MSCs (1 × 107 cells/kg). Lung injury severity, cellular infiltration, and E. coli colony counts were assessed after 48 h. The effects and mechanisms of action of IL-10 UC-MSCs on macrophage function in septic rodents and in humans were subsequently assessed. Survival increased with IL-10 (9/11 (82%)) and naïve (11/12 (91%)) UC-MSCs compared to vehicle (9/15 (60%, p = 0.03). IL-10 UC-MSCs—but not naïve UC-MSCs—significantly decreased the alveolar arterial gradient (455 ± 93 and 520 ± 81, mmHg, respectively) compared to that of vehicle animals (544 ± 52, p = 0.02). Lung tissue bacterial counts were significantly increased in vehicle- and naïve-UC-MSC-treated animals but were not different from sham animals in those treated with IL-10 overexpressing UC-MSCs. IL-10 (but not naïve) UC-MSCs decreased alveolar neutrophils and increased alveolar macrophage percentages compared to vehicle. IL-10 UC-MSCs decreased structural lung injury compared to naïve UC-MSC or vehicle therapy. Alveolar macrophages from IL-10-UC-MSC-treated rats and from human volunteers demonstrated enhanced phagocytic capacity. This was mediated via increased macrophage hemeoxygenase-1, an effect blocked by prostaglandin E2 and lipoxygenase A4 blockade. IL-10 overexpression in UC-MSCs enhanced their effects in E. coli pneumosepsis and increased macrophage function. IL-10 UC-MSCs similarly enhanced human macrophage function, illustrating their therapeutic potential for infection-induced acute respiratory distress syndrome (ARDS).

scholarly journals Evaluation of epithelial progenitor cells and growth factors in a preclinical model of wound healing induced by mesenchymal stromal cells

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Giselle Ramos-Gonzalez ◽  
Olga Wittig ◽  
Dylana Diaz-Solano ◽  
Lianeth Salazar ◽  
Carlos Ayala-Grosso ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Growth Factor ◽  
Progenitor Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Skin Wound ◽  
Preclinical Model ◽  
Human Mscs ◽  
Epithelial Progenitor Cells

Abstract Background: Skin wounds continue to be a global health problem. Several cellular therapy protocols have been used to improve and accelerate skin wound healing. Here, we evaluated the effect of transplantation of mesenchymal stromal cells (MSC) on the wound re-epithelialization process and its possible relationship with the presence of epithelial progenitor cells (EPC) and the expression of growth factors. Methods: An experimental wound model was developed in C57BL/6 mice. Human MSCs seeded on collagen membranes (CM) were implanted on wounds. As controls, animals with wounds without treatment or treated with CM were established. Histological and immunohistochemical (IH) studies were performed at day 3 post-treatment to detect early skin wound changes associated with the presence of EPC expressing Lgr6 and CD34 markers and the expression of keratinocyte growth factor (KGF) and basic fibroblast growth factor (bFGF). Results: MSC transplantation enhanced skin wound re-epithelialization, as compared with controls. It was associated with an increase in Lgr6+ and CD34+ cells and the expression of KGF and bFGF in the wound bed. Conclusion: Our results show that cutaneous wound healing induced by MSC is associated with an increase in EPC and growth factors. These preclinical results support the possible clinical use of MSC to treat cutaneous wounds.

scholarly journals Mesenchymal Stromal Cells and Cutaneous Wound Healing: A Comprehensive Review of the Background, Role, and Therapeutic Potential

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Michael S. Hu ◽  
Mimi R. Borrelli ◽  
H. Peter Lorenz ◽  
Michael T. Longaker ◽  
Derrick C. Wan
Keyword(s):  
Wound Healing ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Wound Repair ◽  
Therapeutic Potential ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Differentiation Potential ◽  
Cutaneous Wound ◽  
Aging Populations

Cutaneous wound repair is a highly coordinated cascade of cellular responses to injury which restores the epidermal integrity and its barrier functions. Even under optimal healing conditions, normal wound repair of adult human skin is imperfect and delayed healing and scarring are frequent occurrences. Dysregulated wound healing is a major concern for global healthcare, and, given the rise in diabetic and aging populations, this medicoeconomic disease burden will continue to rise. Therapies to reliably improve nonhealing wounds and reduce scarring are currently unavailable. Mesenchymal stromal cells (MSCs) have emerged as a powerful technique to improve skin wound healing. Their differentiation potential, ease of harvest, low immunogenicity, and integral role in native wound healing physiology make MSCs an attractive therapeutic remedy. MSCs promote cell migration, angiogenesis, epithelialization, and granulation tissue formation, which result in accelerated wound closure. MSCs encourage a regenerative, rather than fibrotic, wound healing microenvironment. Recent translational research efforts using modern bioengineering approaches have made progress in creating novel techniques for stromal cell delivery into healing wounds. This paper discusses experimental applications of various stromal cells to promote wound healing and discusses the novel methods used to increase MSC delivery and efficacy.

scholarly journals The Effect of Wharton Jelly-Derived Mesenchymal Stromal Cells and Their Conditioned Media in the Treatment of a Rat Spinal Cord Injury

2019 ◽  
Vol 20 (18) ◽  
pp. 4516 ◽  
Author(s):  
Milada Chudickova ◽  
Irena Vackova ◽  
Lucia Machova Urdzikova ◽  
Pavlina Jancova ◽  
Kristyna Kekulova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Transplantation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Immunological Response ◽  
Conditioned Media ◽  
Saline Control ◽  
Cord Injury

The transplantation of Wharton’s jelly derived mesenchymal stromal cells (WJ-MSCs) possesses therapeutic potential for the treatment of a spinal cord injury (SCI). Generally, the main effect of MSCs is mediated by their paracrine potential. Therefore, application of WJ-MSC derived conditioned media (CM) is an acknowledged approach for how to bypass the limited survival of transplanted cells. In this study, we compared the effect of human WJ-MSCs and their CM in the treatment of SCI in rats. WJ-MSCs and their CM were intrathecally transplanted in the three consecutive weeks following the induction of a balloon compression lesion. Behavioral analyses were carried out up to 9 weeks after the SCI and revealed significant improvement after the treatment with WJ-MSCs and CM, compared to the saline control. Both WJ-MSCs and CM treatment resulted in a higher amount of spared gray and white matter and enhanced expression of genes related to axonal growth. However, only the CM treatment further improved axonal sprouting and reduced the number of reactive astrocytes in the lesion area. On the other hand, WJ-MSCs enhanced the expression of inflammatory and chemotactic markers in plasma, which indicates a systemic immunological response to xenogeneic cell transplantation. Our results confirmed that WJ-MSC derived CM offer an alternative to direct stem cell transplantation for the treatment of SCI.

Human marrow-derived mesenchymal stromal cells decrease cisplatin renotoxicity in vitro and in vivo and enhance survival of mice post-intraperitoneal injection

2010 ◽  
Vol 299 (6) ◽  
pp. F1288-F1298 ◽  
Author(s):  
Nicoletta Eliopoulos ◽  
Jing Zhao ◽  
Manaf Bouchentouf ◽  
Kathy Forner ◽  
Elena Birman ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Human Kidney ◽  
Chemotherapeutic Agents ◽  
Human Mscs ◽  
Proliferating Cells ◽  
Phosphorylated Akt

Acute kidney injury (AKI) can occur from the toxic side-effects of chemotherapeutic agents such as cisplatin. Bone marrow-derived mesenchymal stromal cells (MSCs) have demonstrated wide therapeutic potential often due to beneficial factors they secrete. The goal of this investigation was to evaluate in vitro the effect of human MSCs (hMSCs) secretome on cisplatin-treated human kidney cells, and in vivo the consequence of hMSCs intraperitoneal (ip) implantation in mice with AKI. Our results revealed that hMSCs-conditioned media improved survival of HK-2 human proximal tubular cells exposed to cisplatin in vitro. This enhanced survival was linked to increased expression of phosphorylated Akt (Ser473) and was reduced by a VEGF-neutralizing antibody. In vivo testing of these hMSCs established that ip administration in NOD-SCID mice decreased cisplatin-induced kidney function impairment, as demonstrated by lower blood urea nitrogen levels and higher survival. In addition, blood phosphorous and amylase levels were also significantly decreased. Moreover, hMSCs reduced the plasma levels of several inflammatory cytokines/chemokines. Immunohistochemical examination of kidneys showed less apoptotic and more proliferating cells. Furthermore, PCR indicated the presence of hMSCs in mouse kidneys, which also showed enhanced expression of phosphorylated Akt. In conclusion, our study reveals that hMSCs can exert prosurvival effects on renal cells in vitro and in vivo, suggests a paracrine contribution for kidney protective abilities of hMSCs delivered ip, and supports their clinical potential in AKI.

scholarly journals Human Mesenchymal Stromal Cells from Different Sources Diverge in Their Expression of Cell Surface Proteins and Display Distinct Differentiation Patterns

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Kourosch C. Elahi ◽  
Gerd Klein ◽  
Meltem Avci-Adali ◽  
Karl D. Sievert ◽  
Sheila MacNeil ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
The Elderly ◽  
Free Cell ◽  
Surface Proteins ◽  
Human Mscs ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Clinical Potential

When germ-free cell cultures became a laboratory routine, hopes were high for using this novel technology for treatment of diseases or replacement of cells in patients suffering from injury, inflammation, or cancer or even refreshing cells in the elderly. Today, more than 50 years after the first successful bone marrow transplantation, clinical application of hematopoietic stem cells is a routine procedure, saving the lives of many every day. However, transplanting other than hematopoietic stem and progenitor cells is still limited to a few applications, and it mainly applies to mesenchymal stromal cells (MSCs) isolated from bone marrow. But research progressed and different trials explore the clinical potential of human MSCs isolated from bone marrow but also from other tissues including adipose tissue. Recently, MSCs isolated from bone marrow (bmMSCs) were shown to be a blend of distinct cells and MSCs isolated from different tissues show besides some common features also some significant differences. This includes the expression of distinct antigens on subsets of MSCs, which was utilized recently to define and separate functionally different subsets from bulk MSCs. We therefore briefly discuss differences found in subsets of human bmMSCs and in MSCs isolated from some other sources and touch upon how this could be utilized for cell-based therapies.

scholarly journals Human Mesenchymal Stromal Cells Enhance Cartilage Healing in a Murine Joint Surface Injury Model

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1999
Author(s):  
Jade Perry ◽  
Anke J. Roelofs ◽  
Claire Mennan ◽  
Helen S. McCarthy ◽  
Alison Richmond ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Cartilage Repair ◽  
Stromal Cells ◽  
Fluorescent Protein ◽  
Joint Surface ◽  
Human Umbilical Cord ◽  
Repair Tissue ◽  
Adult Mice ◽  
Chondral Defects ◽  
Repair Mechanisms

Human umbilical cord (hUC)- or bone marrow (hBM)-derived mesenchymal stromal cells (MSCs) were evaluated as an allogeneic source of cells for cartilage repair. We aimed to determine if they could enhance healing of chondral defects with or without the recruitment of endogenous cells. hMSCs were applied into a focal joint surface injury in knees of adult mice expressing tdTomato fluorescent protein in cells descending from Gdf5-expressing embryonic joint interzone cells. Three experimental groups were used: (i) hUC-MSCs, (ii) hBM-MSCs and (iii) PBS (vehicle) without cells. Cartilage repair was assessed after 8 weeks and tdTomato-expressing cells were detected by immunostaining. Plasma levels of pro-inflammatory mediators and other markers were measured by electrochemiluminescence. Both hUC-MSC (n = 14, p = 0.009) and hBM-MSC (n = 13, p = 0.006) treatment groups had significantly improved cartilage repair compared to controls (n = 18). While hMSCs were not detectable in the repair tissue at 8 weeks post-implantation, increased endogenous Gdf5-lineage cells were detected in repair tissue of hUC-MSC-treated mice. This xenogeneic study indicates that hMSCs enhance intrinsic cartilage repair mechanisms in mice. Hence, hMSCs, particularly the more proliferative hUC-MSCs, could represent an attractive allogeneic cell population for treating patients with chondral defects and perhaps prevent the onset and progression of osteoarthritis.

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