Chondrogenesis by chemotactic homing of synovium, bone marrow, and adipose stem cells in vitro

Cell transplantation has been well explored for cartilage regeneration. We recently showed that the entire articular surface of a synovial joint can regenerate by endogenous cell homing and without cell transplantation. However, the sources of endogenous cells that regenerate articular cartilage remain elusive. Here, we studied whether cytokines not only chemotactically recruit adipose stem cells (ASCs), mesenchymal stem cells (MSCs), and synovium stem cells (SSCs) but also induce chondrogenesis of the recruited cells. Recombinant human transforming growth factor‐β3 (TGF‐β3; 100 ng) and/or recombinant human stromal derived factor‐1β (SDF‐1β; 100 ng) was control released into an acellular collagen sponge cube with underlying ASCs, MSCs, or SSCs in monolayer culture. Although all cell types randomly migrated into the acellular collagen sponge cube, TGF‐β3 and/or SDF‐1β recruited significantly more cells than the cytokine‐free control group. In 6 wk, TGF‐β3 alone recruited substantial numbers of ASCs (558±65) and MSCs (302±52), whereas codelivery of TGF‐β3 and SDF‐1β was particularly chemotactic to SSCs (400±120). Proliferation of the recruited cells accounted for some, but far from all, of the observed cellularity. TGF‐β3 and SDF‐1β codelivery induced significantly higher aggrecan gene expression than the cytokine‐free group for ASCs, MSCs, and SSCs. Type II collagen gene expression was also significantly higher for ASCs and SSCs by SDF‐1 and TGF‐β3 codelivery. Remarkably, the expression of aggrecan and type II collagen was detected among all cell types. Thus, homing of multiple stem/progenitor cell populations may potentially serve as an alternative or adjunctive approach to cell transplantation for cartilage regeneration.—Mendelson, A., Frank, E., Allred, C., Jones, E., Chen, M., Zhao, W., Mao, J. J. Chondrogenesis by chemotactic homing of synovium, bone marrow, and adipose stem cells in vitro. FASEB J. 25, 3496–3504 (2011). www.fasebj.org

[1]  K. Ting,et al.  Delayed wound closure in fibromodulin-deficient mice is associated with increased TGF-β3 signaling. , 2011, The Journal of investigative dermatology.

[2]  Boon Chin Heng,et al.  The effect of incorporation of exogenous stromal cell-derived factor-1 alpha within a knitted silk-collagen sponge scaffold on tendon regeneration. , 2010, Biomaterials.

[3]  S. Marlovits,et al.  FGF-2 abolishes the chondrogenic effect of combined BMP-6 and TGF-beta in human adipose derived stem cells. , 2010, Journal of biomedical materials research. Part A.

[4]  Jinghua Hao,et al.  Chondrogenesis of synovium-derived mesenchymal stem cells in gene-transferred co-culture system. , 2010, Biomaterials.

[5]  Hai Yao,et al.  Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study , 2010, The Lancet.

[6]  J. Mao,et al.  Hybrid adipogenic implants from adipose stem cells for soft tissue reconstruction in vivo. , 2010, Tissue engineering. Part A.

[7]  Chang Hun Lee,et al.  Regeneration of dental-pulp-like tissue by chemotaxis-induced cell homing. , 2010, Tissue engineering. Part A.

[8]  Stephen D. Thorpe,et al.  The Response of Bone Marrow-Derived Mesenchymal Stem Cells to Dynamic Compression Following TGF-β3 Induced Chondrogenic Differentiation , 2010, Annals of Biomedical Engineering.

[9]  Esmaiel Jabbari,et al.  Migration of marrow stromal cells in response to sustained release of stromal-derived factor-1alpha from poly(lactide ethylene oxide fumarate) hydrogels. , 2010, International journal of pharmaceutics.

[10]  Chang Hun Lee,et al.  Facial reconstruction by biosurgery: cell transplantation versus cell homing. , 2010, Tissue engineering. Part B, Reviews.

[11]  P. Emery,et al.  Mesenchymal stem cells in rheumatoid synovium: enumeration and functional assessment in relation to synovial inflammation level , 2009, Annals of the rheumatic diseases.

[12]  V. Agrawal,et al.  Epimorphic regeneration approach to tissue replacement in adult mammals , 2009, Proceedings of the National Academy of Sciences.

[13]  Scott Hollister,et al.  Tissue formation and vascularization in anatomically shaped human joint condyle ectopically in vivo. , 2009, Tissue engineering. Part A.

[14]  F. Dell’Accio,et al.  Distinct mesenchymal progenitor cell subsets in the adult human synovium. , 2009, Rheumatology.

[15]  J. Feijen,et al.  In vivo recruitment of hematopoietic cells using stromal cell-derived factor 1 alpha-loaded heparinized three-dimensional collagen scaffolds. , 2009, Tissue engineering. Part A.

[16]  Jae H Park,et al.  Biological characterization of long-term cultured human mesenchymal stem cells , 2009, Archives of pharmacal research.

[17]  M. Longaker,et al.  IFATS Collection: Adipose Stromal Cells Adopt a Proangiogenic Phenotype Under the Influence of Hypoxia , 2009, Stem cells.

[18]  D. Link,et al.  Suppression of CXCL12 production by bone marrow osteoblasts is a common and critical pathway for cytokine-induced mobilization. , 2007, Blood.

[19]  Regina Brunauer,et al.  Controversial issue: Is it safe to employ mesenchymal stem cells in cell-based therapies? , 2008, Experimental Gerontology.

[20]  S. Fukuda,et al.  Chemokine-mobilized adult stem cells; defining a better hematopoietic graft , 2008, Leukemia.

[21]  K. Yun,et al.  Inducing chondrogenic differentiation in injectable hydrogels embedded with rabbit chondrocytes and growth factor for neocartilage formation. , 2008, Journal of bioscience and bioengineering.

[22]  Jason A Burdick,et al.  Engineering cartilage tissue. , 2008, Advanced drug delivery reviews.

[23]  F. Luyten,et al.  A biomarker-based mathematical model to predict bone-forming potency of human synovial and periosteal mesenchymal stem cells. , 2008, Arthritis and rheumatism.

[24]  J. Schantz,et al.  Cell guidance in tissue engineering: SDF-1 mediates site-directed homing of mesenchymal stem cells within three-dimensional polycaprolactone scaffolds. , 2007, Tissue engineering.

[25]  Anoop Kumar,et al.  Positional identity of adult stem cells in salamander limb regeneration. , 2007, Comptes rendus biologies.

[26]  Yao‐Hua Song,et al.  Insulin-like growth factor 1 enhances the migratory capacity of mesenchymal stem cells. , 2007, Biochemical and biophysical research communications.

[27]  J. Yao,et al.  Stem cells for tissue engineering of articular cartilage , 2007, Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine.

[28]  D. Scadden,et al.  Stromal Cell‐Derived Factor‐1/CXCR4 Signaling Modifies the Capillary‐Like Organization of Human Embryonic Stem Cell‐Derived Endothelium In Vitro , 2007, Stem cells.

[29]  Ling Qin,et al.  Porous gelatin-chondroitin-hyaluronate tri-copolymer scaffold containing microspheres loaded with TGF-beta1 induces differentiation of mesenchymal stem cells in vivo for enhancing cartilage repair. , 2006, Journal of biomedical materials research. Part A.

[30]  M. Ratajczak,et al.  Migration of Bone Marrow and Cord Blood Mesenchymal Stem Cells In Vitro Is Regulated by Stromal‐Derived Factor‐1‐CXCR4 and Hepatocyte Growth Factor‐c‐met Axes and Involves Matrix Metalloproteinases , 2006, Stem cells.

[31]  J. Mao,et al.  Mesenchymal stem cells and tissue engineering. , 2006, Methods in enzymology.

[32]  A. Seifalian,et al.  Advancing cartilage tissue engineering: the application of stem cell technology. , 2005, Current opinion in biotechnology.

[33]  J. Mao.  Stem‐cell‐driven regeneration of synovial joints , 2005, Biology of the cell.

[34]  J. Cigudosa,et al.  Spontaneous human adult stem cell transformation. , 2005, Cancer research.

[35]  Adel Alhadlaq,et al.  Adult Stem Cell Driven Genesis of Human-Shaped Articular Condyle , 2004, Annals of Biomedical Engineering.

[36]  Farshid Guilak,et al.  Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds. , 2004, Biomaterials.

[37]  Ilyas M. Khan,et al.  The surface of articular cartilage contains a progenitor cell population , 2004, Journal of Cell Science.

[38]  P. Emery,et al.  Enumeration and phenotypic characterization of synovial fluid multipotential mesenchymal progenitor cells in inflammatory and degenerative arthritis , 2003, Arthritis and rheumatism.

[39]  R. Borzì,et al.  A role for chemokines in the induction of chondrocyte phenotype modulation. , 2004, Arthritis and rheumatism.

[40]  W. Fodor.  Tissue engineering and cell based therapies, from the bench to the clinic: The potential to replace, repair and regenerate , 2003, Reproductive biology and endocrinology : RB&E.

[41]  Takashi Inamoto,et al.  Adipose tissue engineering based on human preadipocytes combined with gelatin microspheres containing basic fibroblast growth factor. , 2003, Biomaterials.

[42]  Ralph Müller,et al.  Repair of bone defects using synthetic mimetics of collagenous extracellular matrices , 2003, Nature Biotechnology.

[43]  Alan Grodzinsky,et al.  Tissue-engineered composites for the repair of large osteochondral defects. , 2002, Arthritis and rheumatism.

[44]  F. Luyten,et al.  Multipotent mesenchymal stem cells from adult human synovial membrane. , 2001, Arthritis and rheumatism.

[45]  W. Knudson,et al.  Cartilage proteoglycans. , 2001, Seminars in cell & developmental biology.

[46]  T. Kipps,et al.  Fibroblast-like synoviocytes support B-cell pseudoemperipolesis via a stromal cell-derived factor-1- and CD106 (VCAM-1)-dependent mechanism. , 2001, The Journal of clinical investigation.

[47]  T. Springer,et al.  The Chemokine SDF-1 Is a Chemoattractant for Human CD34+ Hematopoietic Progenitor Cells and Provides a New Mechanism to Explain the Mobilization of CD34+ Progenitors to Peripheral Blood , 1997, The Journal of experimental medicine.

[48]  P. Benya,et al.  Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels , 1982, Cell.