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Mesenchymal stem cells in the treatment of traumatic articular cartilage defects: a comprehensive review.

Bornes TD, Adesida AB, Jomha NM - Arthritis Res. Ther. (2014)

Bottom Line: MSCs are historically harvested through bone marrow aspiration, which does not require invasive surgical intervention or cartilage extraction from other sites as required by other cell-based strategies.A number of specific transplantation protocols have successfully resurfaced articular cartilage in animals and humans to date.This will allow for further optimization of MSC proliferation, chondrogenic differentiation, bioengineered cartilage integration, and clinical outcome.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, University of Alberta, Laboratory of Stem Cell Biology and Orthopaedic Tissue Engineering, Edmonton T6G 2E1, Alberta, Canada.

ABSTRACT
Articular cartilage has a limited capacity to repair following injury. Early intervention is required to prevent progression of focal traumatic chondral and osteochondral defects to advanced cartilage degeneration and osteoarthritis. Novel cell-based tissue engineering techniques have been proposed with the goal of resurfacing defects with bioengineered tissue that recapitulates the properties of hyaline cartilage and integrates into native tissue. Transplantation of mesenchymal stem cells (MSCs) is a promising strategy given the high proliferative capacity of MSCs and their potential to differentiate into cartilage-producing cells - chondrocytes. MSCs are historically harvested through bone marrow aspiration, which does not require invasive surgical intervention or cartilage extraction from other sites as required by other cell-based strategies. Biomaterial matrices are commonly used in conjunction with MSCs to aid cell delivery and support chondrogenic differentiation, functional extracellular matrix formation and three-dimensional tissue development. A number of specific transplantation protocols have successfully resurfaced articular cartilage in animals and humans to date. In the clinical literature, MSC-seeded scaffolds have filled a majority of defects with integrated hyaline-like cartilage repair tissue based on arthroscopic, histologic and imaging assessment. Positive functional outcomes have been reported at 12 to 48 months post-implantation, but future work is required to assess long-term outcomes with respect to other treatment modalities. Despite relatively positive outcomes, further investigation is required to establish a consensus on techniques for treatment of chondral and osteochondral defects with respect to cell source, isolation and expansion, implantation density, in vitro precultivation, and scaffold composition. This will allow for further optimization of MSC proliferation, chondrogenic differentiation, bioengineered cartilage integration, and clinical outcome.

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Mesenchymal stem cell transplantation constructs and protocols. (A) In bone marrow-derived cell (BMDC) transplantation, the bone marrow aspirate is centrifuged to create a BMDC concentrate that contains mesenchymal stem cells (MSCs) within a pool of other cells and chemical mediators. BMDCs are then seeded onto a scaffold and implanted within a cartilage defect. (B,C) MSC transplantation involves isolating MSCs from a bone marrow aspirate by plastic adherence and expansion in plastic tissue culture flasks. MSCs are then seeded onto a scaffold and implanted (B) or precultivated in vitro to promote chondrogenesis prior to implantation (C).
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Fig2: Mesenchymal stem cell transplantation constructs and protocols. (A) In bone marrow-derived cell (BMDC) transplantation, the bone marrow aspirate is centrifuged to create a BMDC concentrate that contains mesenchymal stem cells (MSCs) within a pool of other cells and chemical mediators. BMDCs are then seeded onto a scaffold and implanted within a cartilage defect. (B,C) MSC transplantation involves isolating MSCs from a bone marrow aspirate by plastic adherence and expansion in plastic tissue culture flasks. MSCs are then seeded onto a scaffold and implanted (B) or precultivated in vitro to promote chondrogenesis prior to implantation (C).

Mentions: The goal of MSC transplantation is to create repair tissue with properties of hyaline cartilage that integrates into surrounding native osteochondral tissue while limiting local and systemic adverse effects. Three general MSC transplantation protocols currently exist (Figure 2). The one-step BMDC transplantation protocol consists of bone marrow aspiration, separation of a nucleated cell population containing MSCs amongst other cells, seeding of these cells on a scaffold, and implantation all within a single operative period [80,81,89–91]. A second protocol involves isolation of MSCs within the laboratory, in vitro expansion, and scaffold seeding shortly before implantation [82–85,88]. The scaffold may be seeded at the time of implantation or within a few days after a short in vitro culture period to promote MSC adherence to the biomaterial [82]. The final protocol utilizes isolated, expanded MSCs that are seeded onto a scaffold and precultivated - or pre-differentiated - in vitro over 2 to 3 weeks to promote chondrogenesis prior to implantation [38,66,72].Figure 2


Mesenchymal stem cells in the treatment of traumatic articular cartilage defects: a comprehensive review.

Bornes TD, Adesida AB, Jomha NM - Arthritis Res. Ther. (2014)

Mesenchymal stem cell transplantation constructs and protocols. (A) In bone marrow-derived cell (BMDC) transplantation, the bone marrow aspirate is centrifuged to create a BMDC concentrate that contains mesenchymal stem cells (MSCs) within a pool of other cells and chemical mediators. BMDCs are then seeded onto a scaffold and implanted within a cartilage defect. (B,C) MSC transplantation involves isolating MSCs from a bone marrow aspirate by plastic adherence and expansion in plastic tissue culture flasks. MSCs are then seeded onto a scaffold and implanted (B) or precultivated in vitro to promote chondrogenesis prior to implantation (C).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4289291&req=5

Fig2: Mesenchymal stem cell transplantation constructs and protocols. (A) In bone marrow-derived cell (BMDC) transplantation, the bone marrow aspirate is centrifuged to create a BMDC concentrate that contains mesenchymal stem cells (MSCs) within a pool of other cells and chemical mediators. BMDCs are then seeded onto a scaffold and implanted within a cartilage defect. (B,C) MSC transplantation involves isolating MSCs from a bone marrow aspirate by plastic adherence and expansion in plastic tissue culture flasks. MSCs are then seeded onto a scaffold and implanted (B) or precultivated in vitro to promote chondrogenesis prior to implantation (C).
Mentions: The goal of MSC transplantation is to create repair tissue with properties of hyaline cartilage that integrates into surrounding native osteochondral tissue while limiting local and systemic adverse effects. Three general MSC transplantation protocols currently exist (Figure 2). The one-step BMDC transplantation protocol consists of bone marrow aspiration, separation of a nucleated cell population containing MSCs amongst other cells, seeding of these cells on a scaffold, and implantation all within a single operative period [80,81,89–91]. A second protocol involves isolation of MSCs within the laboratory, in vitro expansion, and scaffold seeding shortly before implantation [82–85,88]. The scaffold may be seeded at the time of implantation or within a few days after a short in vitro culture period to promote MSC adherence to the biomaterial [82]. The final protocol utilizes isolated, expanded MSCs that are seeded onto a scaffold and precultivated - or pre-differentiated - in vitro over 2 to 3 weeks to promote chondrogenesis prior to implantation [38,66,72].Figure 2

Bottom Line: MSCs are historically harvested through bone marrow aspiration, which does not require invasive surgical intervention or cartilage extraction from other sites as required by other cell-based strategies.A number of specific transplantation protocols have successfully resurfaced articular cartilage in animals and humans to date.This will allow for further optimization of MSC proliferation, chondrogenic differentiation, bioengineered cartilage integration, and clinical outcome.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, University of Alberta, Laboratory of Stem Cell Biology and Orthopaedic Tissue Engineering, Edmonton T6G 2E1, Alberta, Canada.

ABSTRACT
Articular cartilage has a limited capacity to repair following injury. Early intervention is required to prevent progression of focal traumatic chondral and osteochondral defects to advanced cartilage degeneration and osteoarthritis. Novel cell-based tissue engineering techniques have been proposed with the goal of resurfacing defects with bioengineered tissue that recapitulates the properties of hyaline cartilage and integrates into native tissue. Transplantation of mesenchymal stem cells (MSCs) is a promising strategy given the high proliferative capacity of MSCs and their potential to differentiate into cartilage-producing cells - chondrocytes. MSCs are historically harvested through bone marrow aspiration, which does not require invasive surgical intervention or cartilage extraction from other sites as required by other cell-based strategies. Biomaterial matrices are commonly used in conjunction with MSCs to aid cell delivery and support chondrogenic differentiation, functional extracellular matrix formation and three-dimensional tissue development. A number of specific transplantation protocols have successfully resurfaced articular cartilage in animals and humans to date. In the clinical literature, MSC-seeded scaffolds have filled a majority of defects with integrated hyaline-like cartilage repair tissue based on arthroscopic, histologic and imaging assessment. Positive functional outcomes have been reported at 12 to 48 months post-implantation, but future work is required to assess long-term outcomes with respect to other treatment modalities. Despite relatively positive outcomes, further investigation is required to establish a consensus on techniques for treatment of chondral and osteochondral defects with respect to cell source, isolation and expansion, implantation density, in vitro precultivation, and scaffold composition. This will allow for further optimization of MSC proliferation, chondrogenic differentiation, bioengineered cartilage integration, and clinical outcome.

Show MeSH
Related in: MedlinePlus