A. Salerno (Liverpool, GB)

University of Liverpool Institute of Lifecourse and Medical Sciences

Presenter Of 1 Presentation

Poster Osteoarthritis

P136 - Investigation of the Regulatory Pathways Involved in Mesenchymal Stem Cell Mediated Cartilage Repair

Presentation Topic
Osteoarthritis
Date
13.04.2022
Lecture Time
09:30 - 09:30
Room
Exhibition Foyer
Session Name
7.3 - Poster Viewing / Coffee Break / Exhibition
Session Type
Poster Session
Disclosure
A patent has been filed to protect some of the findings reported here.

Abstract

Purpose

The chondrogenic capacity of Mesenchymal Stem Cells (MSCs) has led to their use to treat traumatic cartilage injuries. However, these cells have also now been shown to promote tissue repair through the release of cytokines and other regulatory molecules. This trophic effect has opened up the possibility of undifferentiated MSCs being used to treat osteoarthritis (OA). The purpose of this study was to explore differences in regulatory pathways involved in chondrogenesis and in trophic repair.

Methods and Materials

MSCs were cultured from passage 0 until they had become senescent. Cells from sample passages were tested for their potency in a cartilage tissue engineering assay as well as in a meniscal cartilage integration assay as a surrogate for trophic repair. Combined genomic and proteomic screening was used to identify regulatory pathways involved.

Results

Bone marrow derived MSCs from 4 donors were allowed to proliferate until growth arrest. The chondrogenic potency of these MSCs fell significantly with passage. However, there was no reduction in trophic repair. From genomic and proteomic analysis, the largest and most significant change identified in relation to the loss of chondrogenesis with increasing passage was in the cell-cycle master regulator FOXM1 gene pathway, with clear evidence for downregulation of the FOXM1 gene itself and with six out of seven of its downstream effectors also predicted to be downregulated. For trophic repair, which remained high throughout all passages, genes and proteins related to cell movement, cell migration and wound healing also remained at a high level across all four passages, consistent with their involvement in trophic mechanisms.

Conclusion

We have demonstrated clear differences in the regulation of chondrogenic and trophic repair pathways of MSCs, demonstrating that these two mechanisms should be considered as separate and distinct therapeutic opportunities. Further exploration of the pathways invovled may help to optimise each of these therapeutic strategies for the treatment of OA in the future.

Collapse

Presenter Of 1 Presentation

Osteoarthritis

P136 - Investigation of the Regulatory Pathways Involved in Mesenchymal Stem Cell Mediated Cartilage Repair

Abstract

Purpose

The chondrogenic capacity of Mesenchymal Stem Cells (MSCs) has led to their use to treat traumatic cartilage injuries. However, these cells have also now been shown to promote tissue repair through the release of cytokines and other regulatory molecules. This trophic effect has opened up the possibility of undifferentiated MSCs being used to treat osteoarthritis (OA). The purpose of this study was to explore differences in regulatory pathways involved in chondrogenesis and in trophic repair.

Methods and Materials

MSCs were cultured from passage 0 until they had become senescent. Cells from sample passages were tested for their potency in a cartilage tissue engineering assay as well as in a meniscal cartilage integration assay as a surrogate for trophic repair. Combined genomic and proteomic screening was used to identify regulatory pathways involved.

Results

Bone marrow derived MSCs from 4 donors were allowed to proliferate until growth arrest. The chondrogenic potency of these MSCs fell significantly with passage. However, there was no reduction in trophic repair. From genomic and proteomic analysis, the largest and most significant change identified in relation to the loss of chondrogenesis with increasing passage was in the cell-cycle master regulator FOXM1 gene pathway, with clear evidence for downregulation of the FOXM1 gene itself and with six out of seven of its downstream effectors also predicted to be downregulated. For trophic repair, which remained high throughout all passages, genes and proteins related to cell movement, cell migration and wound healing also remained at a high level across all four passages, consistent with their involvement in trophic mechanisms.

Conclusion

We have demonstrated clear differences in the regulation of chondrogenic and trophic repair pathways of MSCs, demonstrating that these two mechanisms should be considered as separate and distinct therapeutic opportunities. Further exploration of the pathways invovled may help to optimise each of these therapeutic strategies for the treatment of OA in the future.

Collapse