The Chondrogenic Potential of Human Bone-Marrow-Derived Mesenchymal Progenitor Cells*

Yoo, Jung U.; Barthel, Traci S.; Nishimura, Keita; Solchaga, Luis A.; Caplan, Arnold I.; Goldberg, Victor M.; Johnstone, Brian

doi:10.2106/00004623-199812000-00004

Cited by 777 publications

(688 citation statements)

References 36 publications

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“…To confirm that the adherent cells were comprised of a significant population of mesenchymal progenitor cells (MSCs), using the method of Johnstone Gene delivery via bone marrow clots A Pascher et al et al 36 portions of the cell cultures were seeded into aggregate culture and incubated in chondrogenic media (serum-free DMEM, ITS þ Premix, 1 mM pyruvate, 37.5 mg/ml ascorbate 2-phosphate and 10 À7 M dexamethasone with 10 ng/ml TGF-b1). Consistent with previous reports, 36,37 histologic sections of the pellets after 21 days in culture showed the presence of abundant extracellular matrix enriched for proteoglycan and collagen type II. For adenoviral infection, monolayer cultures of the MSCs were grown to B90% confluence in 75 cm 2 flasks and were incubated with 10 11 vp Ad.GFP in a minimal volume of serum-free DMEM at 371C and 5% CO 2 .…”

Section: Generation Of Cell-supplemented Bone Marrow Clotssupporting

confidence: 91%

Gene delivery to cartilage defects using coagulated bone marrow aspirate

et al. 2004

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The long-term goal of the present study is to develop a clinically applicable approach to enhance natural repair mechanisms within cartilage lesions by targeting bone marrow-derived cells for genetic modification. To determine if bone marrow-derived cells infiltrating osteochondral defects could be transduced in situ, we implanted collagen-glycosaminoglycan (CG) matrices preloaded with adenoviral vectors containing various marker genes into lesions surgically generated in rabbit femoral condyles. Analysis of the recovered implants showed transgenic expression up to 21 days; however, a considerable portion was found in the synovial lining, indicating leakage of the vector and/or transduced cells from the matrix. As an alternative medium for gene delivery, we investigated the feasibility of using coagulated bone marrow aspirates. Mixture of an adenoviral suspension with the fluid phase of freshly aspirated bone marrow resulted in uniform dispersion of the vector throughout, and levels of transgenic expression in direct proportion to the density of nucleated cells in the ensuing clot. Furthermore, cultures of mesenchymal progenitor cells, previously transduced ex vivo with recombinant adenovirus, were readily incorporated into the coagulate when mixed with fresh aspirate. These vector-seeded and cell-seeded bone marrow clots were found to maintain their structural integrity following extensive culture and maintained transgenic expression in this manner for several weeks. When used in place of the CG matrix as a gene delivery vehicle in vivo, genetically modified bone marrow clots were able to generate similarly high levels of transgenic expression in osteochondral defects with better containment of the vector within the defect. Our results suggest that coagulates formed from aspirated bone marrow may be useful as a means of gene delivery to cartilage and perhaps other musculoskeletal tissues. Cells within the fluid can be readily modified with an adenoviral vector, and the matrix formed from the clot is completely natural, native to the host and is the fundamental platform on which healing and repair of mesenchymal tissues is based.

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Section: Generation Of Cell-supplemented Bone Marrow Clotssupporting

confidence: 91%

Gene delivery to cartilage defects using coagulated bone marrow aspirate

et al. 2004

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“…These are multipotent adult progenitor cells that are capable of differentiating into bone, 18 cartilage, 19 muscle 20 tendon and ligament, 21 and fat cell 7 phenotypes. The demonstrated ability of MSCs to differentiate into different phenotypes makes MSCs excellent candidates as therapeutic cells for the repair of damaged tissue.…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Migration, fate and in vivo imaging of adult stem cells in the CNS

Syková

Jendelová

2007

Cell Death Differ

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“…The principal candidates for such therapies are the mesenchymal stem cells (MSCs), which are present in a number of tissues and can be extracted from bone marrow, adipose tissue, synovial membrane and umbilical cord tissue [10]. MSCs have a high proliferative capacity [11] and have the ability to differentiate into several cell types [12], including adipocytes [13], osteocytes [14] and chondrocytes [15], although their differentiation potential diminishes with passages in vitro [16]. As NP cells have a similar morphology and gene expression profile to articular chondrocytes, one can presume that MSCs might be able to differentiate into NP cells.…”

Section: Introductionmentioning

confidence: 99%

Influence of different commercial scaffolds on the in vitro differentiation of human mesenchymal stem cells to nucleus pulposus-like cells

et al. 2011

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Introduction Cell-based therapies for regeneration of the degenerated intervertebral disc (IVD) are an alternative to current surgical intervention. Mesenchymal stem cells (MSCs), in combination with a scaffold, might be ideal candidates for regenerating nucleus pulposus (NP), the pressure-distributing part of the IVD. While the use of growth factors for MSCs differentiation currently receives major attention, in this study we compare the performance of sponge-like matrixes in supporting cell differentiation into NP-like cells. Materials and methods Four types matrixes approved as medical devices for other applications were tested as scaffolds for MSCs: two made of equine or porcine collagen, one of gelatin and one of chitosan. Bone marrowderived human MSCs were seeded in these scaffolds or embedded in alginate, as a three-dimensional control. After five weeks in culture, NP-like differentiation of the cellscaffold constructs was analyzed by qRT-PCR, histology, total DNA quantification, proteoglycan accumulation and immunohistochemistry. Results MSCs in collagen matrixes and gelatin produced more mRNA and proteins of the chondrogenic markers collagen type I, collagen type II (COL2) and aggrecan (ACAN), when compared with cells embedded in alginate or chitosan. Proteoglycan accumulation and cell survival were also higher in collagen and gelatin matrixes. Gene expression results were also confirmed by histological and immunohistochemical staining. In contrast to alginate control, the gene expression of the undesired bone marker osteopontin was lower in all tested groups. In porcine collagen supports, MSC expression ratio between COL2/ ACAN closely resembled the expression of nucleus pulposus cells, but gene expression of recently described NP markers keratin19, PAX1 and FOXF1 was lower. Conclusions Collagen supports provide a readily available, medically approved and effective scaffold for chondrogenic differentiation in vitro, but the phenotype of differentiated MSCs is not yet completely equivalent to that of NP cells.

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The Chondrogenic Potential of Human Bone-Marrow-Derived Mesenchymal Progenitor Cells*

Cited by 777 publications

References 36 publications

Gene delivery to cartilage defects using coagulated bone marrow aspirate

Gene delivery to cartilage defects using coagulated bone marrow aspirate

Migration, fate and in vivo imaging of adult stem cells in the CNS

Influence of different commercial scaffolds on the in vitro differentiation of human mesenchymal stem cells to nucleus pulposus-like cells

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