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

Jade Perry; Anke J. Roelofs; Claire Mennan; Helen S. McCarthy; Alison Richmond; Susan M. Clark; Anna H. K. Riemen; Karina Wright; Cosimo De Bari; Sally Roberts

doi:10.3390/cells10081999

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

Jade Perry^*, Anke J. Roelofs, Claire Mennan, Helen S. McCarthy, Alison Richmond, Susan M. Clark, Anna H. K. Riemen, Karina Wright, Cosimo De Bari, Sally Roberts

^*Corresponding author for this work

Tissue Engineering & Regenerative Therapies Centre, Versus Arthritis

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

5 Downloads (Pure)

Abstract

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.

Original language	English
Article number	1999
Number of pages	16
Journal	Cells
Volume	10
Issue number	8
DOIs	https://doi.org/10.3390/cells10081999
Publication status	Published - 6 Aug 2021

Bibliographical note

Funding: This research was funded by Versus Arthritis, grant numbers 18480, 19429 and 21156, and the Medical Research Council, grant number MR/L010453/1.
Acknowledgments: We thank Pat Evans and Martin Pritchard, Histopathology Dept, RJAH Orthopaedic Hospital, for guidance on histology; Meso Scale Diagnostics, LLC for advice and the loan of equipment for analyte analyses; all members of the Arthritis and Regenerative Medicine Laboratory at the University of Aberdeen, particularly Hui Wang, Sharon Ansboro and Ausra Lionikiene for their help with mouse surgeries and tissue collection, as well as staff at the University of Aberdeen’s
animal facility and microscopy and hystology facility for their support

Keywords

mesenchymal stromal cells
umbilical cord
bone marrow
cartilage repair
allogeneic cell therapy
osteoarthritis
mouse models

Access to Document

10.3390/cells10081999Licence: CC BY

Perry_etal_CELLS_Human_mesenchymal_stromal_VOR
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Final published version, 4.01 MBLicence: CC BY

Cite this

@article{7639a3ccaa90458186623927bc026e00,

title = "Human Mesenchymal Stromal Cells Enhance Cartilage Healing in a Murine Joint Surface Injury Model",

abstract = "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.",

keywords = "mesenchymal stromal cells, umbilical cord, bone marrow, cartilage repair, allogeneic cell therapy, osteoarthritis, mouse models",

author = "Jade Perry and Roelofs, {Anke J.} and Claire Mennan and McCarthy, {Helen S.} and Alison Richmond and Clark, {Susan M.} and Riemen, {Anna H. K.} and Karina Wright and {De Bari}, Cosimo and Sally Roberts",

note = "Funding: This research was funded by Versus Arthritis, grant numbers 18480, 19429 and 21156, and the Medical Research Council, grant number MR/L010453/1. Acknowledgments: We thank Pat Evans and Martin Pritchard, Histopathology Dept, RJAH Orthopaedic Hospital, for guidance on histology; Meso Scale Diagnostics, LLC for advice and the loan of equipment for analyte analyses; all members of the Arthritis and Regenerative Medicine Laboratory at the University of Aberdeen, particularly Hui Wang, Sharon Ansboro and Ausra Lionikiene for their help with mouse surgeries and tissue collection, as well as staff at the University of Aberdeen{\textquoteright}s animal facility and microscopy and hystology facility for their support",

year = "2021",

month = aug,

day = "6",

doi = "10.3390/cells10081999",

language = "English",

volume = "10",

journal = "Cells",

issn = "2073-4409",

publisher = "MDPI",

number = "8",

}

TY - JOUR

T1 - Human Mesenchymal Stromal Cells Enhance Cartilage Healing in a Murine Joint Surface Injury Model

AU - Perry, Jade

AU - Roelofs, Anke J.

AU - Mennan, Claire

AU - McCarthy, Helen S.

AU - Richmond, Alison

AU - Clark, Susan M.

AU - Riemen, Anna H. K.

AU - Wright, Karina

AU - De Bari, Cosimo

AU - Roberts, Sally

N1 - Funding: This research was funded by Versus Arthritis, grant numbers 18480, 19429 and 21156, and the Medical Research Council, grant number MR/L010453/1. Acknowledgments: We thank Pat Evans and Martin Pritchard, Histopathology Dept, RJAH Orthopaedic Hospital, for guidance on histology; Meso Scale Diagnostics, LLC for advice and the loan of equipment for analyte analyses; all members of the Arthritis and Regenerative Medicine Laboratory at the University of Aberdeen, particularly Hui Wang, Sharon Ansboro and Ausra Lionikiene for their help with mouse surgeries and tissue collection, as well as staff at the University of Aberdeen’s animal facility and microscopy and hystology facility for their support

PY - 2021/8/6

Y1 - 2021/8/6

N2 - 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.

AB - 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.

KW - mesenchymal stromal cells

KW - umbilical cord

KW - bone marrow

KW - cartilage repair

KW - allogeneic cell therapy

KW - osteoarthritis

KW - mouse models

U2 - 10.3390/cells10081999

DO - 10.3390/cells10081999

M3 - Article

SN - 2073-4409

VL - 10

JO - Cells

JF - Cells

IS - 8

M1 - 1999

ER -

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

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this