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

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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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

Cells Tissues Organs ◽

10.1159/000513895 ◽

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> < 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.

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Combining canine mesenchymal stromal cells and hyaluronic acid for cartilage repair

Genetics and Molecular Biology ◽

10.1590/1678-4685-gmb-2019-0275 ◽

2020 ◽

Vol 43 (1) ◽

Author(s):

Maria Inês Wits ◽

Gabriela Cabanas Tobin ◽

Maiele Dornelles Silveira ◽

Karine Gehlen Baja ◽

Luisa Maria Macedo Braga ◽

...

Keyword(s):

Hyaluronic Acid ◽

Mesenchymal Stromal Cells ◽

Cartilage Repair ◽

Stromal Cells

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Continuous Low-Intensity Ultrasound Preserves Mitochondrial Potential, Inhibits NFκB Activation and Rescues Chondrogenesis of Mesenchymal Stromal Cells

10.21203/rs.3.rs-342462/v1 ◽

2021 ◽

Author(s):

Sarayu Bhogoju ◽

Shahid Khan ◽

Denzhi Wang ◽

Anuradha Subramanian

Keyword(s):

Mesenchymal Stromal Cells ◽

Cartilage Repair ◽

Stromal Cells ◽

Nuclear Translocation ◽

Feedback Mechanism ◽

Protective Agent ◽

Mitochondrial Potential ◽

Qrt Pcr ◽

Low Intensity ◽

Low Intensity Ultrasound

Abstract Objective: Dysregulation of the anabolic processes in a proinflammatory joint environment coupled with impeded chondrogenic differentiation of mesenchymal stromal cells (MSCs) led to inferior cartilage repair outcomes. The preponderance of proinflammatory cytokines activated nuclear factor kappa B (NFκB) and impeded the chondrogenesis of MSCs. Thus, strategies that minimize the deleterious effects of activated NFκB while promoting MSC chondrogenesis are of interest. The present study establishes the ability of continuous low-intensity ultrasound (cLIUS) to rescue MSC chondrogenesis impacted by a proinflammatory environment. Methods: Human bone marrow-derived MSCs were seeded in alginate:collagen hydrogels and cultured for 21-days in an ultrasound-assisted bioreactor 14 kPa (5.0 MHz, 2.5 Vpp; 4-applications/day) for 21 days in the presence of IL1β and evaluated by qRT-PCR (n=10), immunofluorescence (n=15), western blotting (WB) (n=6), and immunohistochemistry (n=3). The differential expression of markers associated with NFκB pathway under cLIUS were evaluated upon a single exposure of cLIUS and assayed by qRT-PCR (n=3), immunofluorescence (n=30-60), WB (n=6) and tetramethylrhodamine methyl ester assay (n=50) was used to assess the mitochondrial potential under IL1β and cLIUS treatment.Results: Chondroinductive potential of cLIUS was preserved as noted by the increased expression of SOX9 and deposition of collagen II. cLIUS extended its chondroprotective effects by stabilizing the NFκB complex in the cytoplasm via engaging the IκBα feedback mechanism, thus preventing its nuclear translocation. cLIUS acted as a mitochondrial protective agent by restoring the mitochondrial potential and the mitochondrial mRNA expression in a proinflammatory environment. Conclusion: Our results demonstrated the potential of cLIUS for cartilage repair and regeneration under proinflammatory conditions.

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A simple, efficient and economical method for isolating and culturing human umbilical cord blood‑derived mesenchymal stromal cells

Molecular Medicine Reports ◽

10.3892/mmr.2019.10767 ◽

2019 ◽

Author(s):

Junhe Zhang ◽

Junli Zhao ◽

Qinwen Mao ◽

Haibin Xia

Keyword(s):

Cord Blood ◽

Umbilical Cord ◽

Mesenchymal Stromal Cells ◽

Umbilical Cord Blood ◽

Stromal Cells ◽

Human Umbilical Cord Blood ◽

Human Umbilical Cord ◽

Economical Method

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Therapeutic effect of human umbilical cord-derived multipotent mesenchymal stromal cells in a patient with Crigler–Najjar syndrome type I

Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) ◽

10.21508/1027-4065-2019-64-4-26-34 ◽

2019 ◽

Vol 64 (4) ◽

pp. 26-34

Author(s):

G. T. Sukhikh ◽

A. V. Degtyareva ◽

D. N. Silachev ◽

K. V. Gorunov ◽

I. V. Dubrovina ◽

...

Keyword(s):

Umbilical Cord ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Multipotent Mesenchymal Stromal Cells ◽

Human Umbilical Cord ◽

Type I ◽

Syndrome Type ◽

Safe Level ◽

Period 2

The article presents the results of intravenous transplantation of allogeneic multipotent mesenchymal stromal cells, derived from a human umbilical cord, to a child with Crigler–Najjarsyndrome type I during the first 2 years of life. The therapy is aimed at reduction of the duration of phototherapy while maintaining a safe level of serum bilirubin.In this study, a five-day-old child with the bilirubin level of 340 µmol/l was treated with phototherapy for 16–18 hours daily in the neonatal period. Then, phototherapy was reduced to 14–16 hours. The level of bilirubin varied from 329 to 407 μmol/l. At the age of 2 months, it was decided to use multipotent mesenchymal stromal cells with a significant decrease in the duration of phototherapy up to 2 hours a day. During the observation period (2 years at the time of writing this article) the child received 6 injections of multipotent mesenchymal stromal cells. A positive effect developed within 4–7 days after administration and persisted for 2–3 months. There were no side effects or complications during and after transplantation.Thus, intravenous transplantation of multipotent mesenchymal stromal cells is an effective treatment of Crigler–Najjar syndrome type I; it reducesthe need for phototherapy,significantly improvesthe quality of life of the patients and prolongstheir life with native liver.

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