Therapeutic potential of non-adherent BM-derived mesenchymal stem cells in tissue regeneration

被引:33
作者
Zhang, Z. L. [3 ,4 ,5 ]
Tong, J. [5 ]
Lu, R. N. [1 ,2 ]
Scutt, A. M. [6 ]
Goltzman, D. [3 ,4 ]
Miao, D. S. [1 ,2 ,3 ,4 ]
机构
[1] Nanjing Med Univ, Inst Dent Res, Stomatol Coll, Nanjing 210029, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Res Ctr Bone & Stem Cells, Dept Anat Histol & Embryol, Nanjing 210029, Jiangsu, Peoples R China
[3] McGill Univ, McGill Univ Hlth Ctr, Calcium Res Lab, Montreal, PQ, Canada
[4] McGill Univ, Dept Med, Montreal, PQ, Canada
[5] Soochow Univ, Dept Publ Hlth, Suzhou, Jiangsu, Peoples R China
[6] Univ Sheffield, Dept Mat Engn, Kroto Res Inst, Sheffield, S Yorkshire, England
基金
英国生物技术与生命科学研究理事会; 中国国家自然科学基金;
关键词
BM mesenchymal stem cells; cell differentiation; irradiation; transplantation; hematopoietic re-construction; MARROW STROMAL CELLS; VITAMIN-D-RECEPTOR; BONE-MARROW; PROGENITOR CELLS; PRECURSOR CELLS; IN-VIVO; PARATHYROID-HORMONE; 25-HYDROXYVITAMIN-D; 1-ALPHA-HYDROXYLASE; HEMATOPOIETIC MICROENVIRONMENT; 1,25-DIHYDROXYVITAMIN D-3;
D O I
10.1038/bmt.2008.260
中图分类号
Q6 [生物物理学];
学科分类号
071011 [生物物理学];
摘要
We demonstrated that non-adherent BM cells (NA-BMCs) can be expanded in suspension and give rise to multiple mesenchymal phenotypes including fibroblastic, osteoblastic, chondrocytic and adipocytic as well as glial cell lineages in vitro using the 'pour-off' BMC culture method. Mesenchymal stem cells (MSCs) derived from NA-BMCs (NA-MSCs) from wild-type mice were transplanted into VDR gene knockout (VDR-/-) mice that had received a lethal dose of radiation. Results revealed that NA-MSC can be used to rescue lethally irradiated mice and become incorporated into a diverse range of tissues. After lethal dose irradiation, all untransplanted mice died within 2 weeks, whereas those transplanted with NA-MSCs were viable for at least 3 months. Transplantation rescued these mice by reconstructing a hematopoietic system and repairing other damaged tissues. WBC, RBC and platelet counts recovered to normal after 1 month, and VDR gene expression was found in various tissues of viable VDR-/- recipients. Adult BM harbors pluripotent NA-MSCs, which can migrate in vivo into multiple body organs. In an appropriate microenvironment, they can adhere, proliferate and differentiate into specialized cells of target tissues and thus function in damaged tissue regeneration and repair.
引用
收藏
页码:69 / 81
页数:13
相关论文
共 57 条
[1]
ENGRAFTMENT OF A CLONAL BONE-MARROW STROMAL CELL-LINE INVIVO STIMULATES HEMATOPOIETIC RECOVERY FROM TOTAL-BODY IRRADIATION [J].
ANKLESARIA, P ;
KASE, K ;
GLOWACKI, J ;
HOLLAND, CA ;
SAKAKEENY, MA ;
WRIGHT, JA ;
FITZGERALD, TJ ;
LEE, CY ;
GREENBERGER, JS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (21) :7681-7685
[2]
Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy [J].
Baksh, D ;
Song, L ;
Tuan, RS .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2004, 8 (03) :301-316
[3]
Proliferation kinetics and differentiation potential of ex vivo expanded human bone marrow stromal cells: Implications for their use in cell therapy [J].
Banfi, A ;
Muraglia, A ;
Dozin, B ;
Mastrogiacomo, M ;
Cancedda, R ;
Quarto, R .
EXPERIMENTAL HEMATOLOGY, 2000, 28 (06) :707-715
[4]
Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo [J].
Bartholomew, A ;
Sturgeon, C ;
Siatskas, M ;
Ferrer, K ;
McIntosh, K ;
Patil, S ;
Hardy, W ;
Devine, S ;
Ucker, D ;
Deans, R ;
Moseley, A ;
Hoffman, R .
EXPERIMENTAL HEMATOLOGY, 2002, 30 (01) :42-48
[5]
Extracellular matrix made by bone marrow cells facilitates expansion of marrow-derived mesenchymal progenitor cells and prevents their differentiation into osteoblasts [J].
Chen, Xiao-Dong ;
Dusevich, Vladimir ;
Feng, Jian Q. ;
Manolagas, Stavros C. ;
Jilka, Robert L. .
JOURNAL OF BONE AND MINERAL RESEARCH, 2007, 22 (12) :1943-1956
[6]
CLARKE E, 1991, EUR J HAEMATOL, V46, P296
[7]
Parathyroid hormone activates adhesion in bone marrow stromal precursor cells [J].
Davies, J ;
Chambers, TJ .
JOURNAL OF ENDOCRINOLOGY, 2004, 180 (03) :505-513
[8]
Tissue engineering with muscle-derived stem cells [J].
Deasy, BM ;
Yong, LI ;
Huard, J .
CURRENT OPINION IN BIOTECHNOLOGY, 2004, 15 (05) :419-423
[9]
Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli [J].
Di Nicola, M ;
Carlo-Stella, C ;
Magni, M ;
Milanesi, M ;
Longoni, PD ;
Matteucci, P ;
Grisanti, S ;
Gianni, AM .
BLOOD, 2002, 99 (10) :3838-3843
[10]
Increased longevity of hematopoiesis in continuous bone marrow cultures and adipocytogenesis in marrow stromal cells derived from Smad3-/- mice [J].
Epperly, MW ;
Cao, S ;
Goff, J ;
Shields, D ;
Zhou, SH ;
Glowacki, J ;
Greenberger, JS .
EXPERIMENTAL HEMATOLOGY, 2005, 33 (03) :353-362