Behavior of transplanted bone marrow-derived mesenchymal stem cells in periodontal defects.

BACKGROUND Recently, there have been an increased number of basic and clinical reports indicating the superior potential of bone marrow-derived mesenchymal stem cells (MSCs) for tissue regeneration. In periodontal treatment, previous animal studies indicated that autotransplantation of bone marrow MSCs into experimental periodontal defects enhanced periodontal tissue regeneration. However, mechanisms for periodontal tissue regeneration with MSCs are still unclear. The purpose of this study was to elucidate the behavior of transplanted MSCs in periodontal defects. METHODS Bone marrow MSCs were isolated from beagle dogs, labeled with green fluorescent protein (GFP), and expanded in vitro. The expanded MSCs were mixed with atelocollagen (2% type I collagen) at final concentrations of 2 x 10(7) cells/ml and transplanted into experimental Class III periodontal defects. Localizations of GFP and proliferating cell nuclear antigen (PCNA)-positive cells were evaluated by immunohistochemical analysis. RESULTS Four weeks after transplantation, the periodontal defects were almost regenerated with periodontal tissue. Cementoblasts, osteoblasts, osteocytes, and fibroblasts of the regenerated periodontal tissue were positive with GFP. PCNA-positive cells were present in regenerating connective tissue. CONCLUSION These findings suggest that transplanted mesenchymal stem cells could survive and differentiate into periodontal tissue cells, resulting in enhancement of periodontal tissue regeneration.

[1]  P. Kramer,et al.  Mesenchymal Stem Cells Acquire Characteristics of Cells in the Periodontal Ligament in vitro , 2004, Journal of dental research.

[2]  Reuben.,et al.  Cell-based tissue engineering therapies: the influence of whole body physiology. , 1998, Advanced drug delivery reviews.

[3]  Taiji Ito,et al.  A New System for Stringent, High-Titer Vesicular Stomatitis Virus G Protein-Pseudotyped Retrovirus Vector Induction by Introduction of Cre Recombinase into Stable Prepackaging Cell Lines , 1998, Journal of Virology.

[4]  Takashi Takata,et al.  Enhancement of periodontal tissue regeneration by transplantation of bone marrow mesenchymal stem cells. , 2004, Journal of periodontology.

[5]  S. Ogawa,et al.  Cardiomyocytes can be generated from marrow stromal cells in vitro. , 1999, The Journal of clinical investigation.

[6]  G. Balian,et al.  Tracing Transduced Cells in Osteochondral Defects , 2003, Journal of pediatric orthopedics.

[7]  K. Satomura,et al.  Circulating Skeletal Stem Cells , 2001, The Journal of cell biology.

[8]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[9]  Fred H. Gage,et al.  Can stem cells cross lineage boundaries? , 2001, Nature Medicine.

[10]  Y. Hirasawa,et al.  Ex vivo gene delivery using an adenovirus vector in treatment for cartilage defects. , 2000, The Journal of rheumatology.

[11]  K. Kraus,et al.  Fluorescently labeled mesenchymal stem cells (MSCs) maintain multilineage potential and can be detected following implantation into articular cartilage defects. , 2002, Biomaterials.

[12]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[13]  A. Vescovi,et al.  Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. , 1999, Science.

[14]  S. Abramson,et al.  Transplantation of adenovirally transduced allogeneic chondrocytes into articular cartilage defects in vivo. , 1997, Osteoarthritis and cartilage.

[15]  R. Deans,et al.  Mesenchymal stem cells: biology and potential clinical uses. , 2000, Experimental hematology.

[16]  T. Kubo,et al.  Behavior of Transplanted Bone Marrow-derived GFP Mesenchymal Cells in Osteochondral Defect as a Simulation of Autologous Transplantation , 2005, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[17]  W. Grzesik,et al.  Cementum and periodontal wound healing and regeneration. , 2002, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[18]  Alan W. Flake,et al.  Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep , 2000, Nature Medicine.

[19]  D J Prockop,et al.  Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Y. Kato,et al.  Retention of multilineage differentiation potential of mesenchymal cells during proliferation in response to FGF. , 2001, Biochemical and biophysical research communications.

[21]  S. Bruder,et al.  Growth kinetics, self‐renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation , 1997, Journal of cellular biochemistry.