Stem cells from periosteum for joint cartilage repair

Janis Kelly

March 29, 2006

Mar 29, 2006

London, UK - Multipotent mesenchymal stem cells (MSCs) that can differentiate into cartilage, muscle, or adipose tissue can be retrieved from adult human periosteum, and small bits of periosteum obtained by biopsy might provide enough MSCs for use in joint resurfacing, Dr Cosimo De Bari (King's College, London, UK) reports in the April 2006 issue of Arthritis & Rheumatism [ 1 ].

"Multipotent MSCs can be obtained from adult human periosteum, and these cells exist regardless of donor age. The findings of this study offer the opportunity for development of regenerative-medicine approaches to repair damaged tissues in rheumatology," De Bari told rheuma wire .


Periosteal MSCs remain multipotent regardless of donor age

De Bari and colleagues used samples of proximal tibia from human donors obtained either within 12 hours of death or at the time of surgical knee replacement because of degenerative osteoarthritis (OA) as a source of periosteum They enzymatically separated the cells, then expanded them and did cell cloning by limiting dilution. The first-passage cells were suspended in growth medium and plated at 0.5 cells/well; this density provides a nearly 95% certainty than the resulting clones would derive from a single periosteal cell progenitor.

Cells were phenotyped by three-color flow cytometry using a variety of cell surface markers to identify cell type. They were also tested for in vitro ability to form adipocytes, chondrocytes, and osteoblasts. Cells transduced with the LacZ marker gene were then injected into mouse tibialis anterior muscle to test for in vivo myogenesis and transplanted into a goat model of joint-surface defect to test ability to repair joint surfaces.

These studies showed that the periosteal MSCs had long-term self-renewal capacity (linear for 30 population doublings, then declining with age) and that they were able to differentiate into adipocytes, skeletal muscle cells able to contribute to muscle regeneration, bone, and cartilage. Although the implanted cells in the goat model did not repair the experimental joint-surface defect, they did form cartilage tissue at the margins of the defect, providing proof of principle that implanted periosteal MSCs can undergo chondrogenesis in vivo.

Of note, the phenotype analysis showed that these abilities were inherent in single cells and were not the result of subsets of already-committed progenitor cells in the periosteal sample.

De Bari said that this suggests a new, readily accessible source for multipotent MSCs that could be used for tissue engineering and regenerative medicine.

Our ultimate goal is the development of consistent and effective MSC-based therapeutic protocols for joint-surface repair.

"A small periosteal biopsy represents a relatively easily accessible source of MSCs," De Bari said. "Our ultimate goal is the development of consistent and effective MSC-based therapeutic protocols for joint-surface repair and, more generally, for skeletal-tissue repair. The next step will be to test purified homogeneous populations of periosteal MSCs with consistent and reproducible biological behaviors in preclinical studies and, at the appropriate time, in clinical studies. These are ongoing efforts in our rheumatology department at King's College London."


Source

  1. De Bari C, Dell'Accio F, Vanlauwe J, et al. Mesenchymal multipotency of adult human periosteal cells demonstrated by single-cell lineage analysis. Arthritis Rheum 2006; 54:1209-1221.

 

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