A niche opportunity for stem cell therapeutics

被引:36
作者
Adams, G. B. [2 ]
Scadden, D. T. [1 ,3 ]
机构
[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA USA
[2] Univ So Calif, Keck Sch Med, Ctr Stem Cell & Regenerat Med, Los Angeles, CA USA
[3] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA USA
关键词
hematopoietic stem cells; niche microenvironment; stem cell therapy; stem cell engraftment; stem cell homing;
D O I
10.1038/sj.gt.3303063
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The success of hematopoietic stem cell (HSC)-based therapies relies on the ability of the stem cells to both engraft and self-renew sufficiently in the bone marrow microenvironment. Previous studies identified that a number of components of bone contribute to the regulation of HSCs indicating that they participate in a stem cell 'niche'. This niche is a dynamic microenvironment that changes during development and with varying physiologic states. Components of it, such as the osteoblast, can be modulated through pharmacological treatment. Reasoning that the stem cell niche may be manipulated to augment the effectiveness of stem cell therapies, we demonstrated that daily treatment with parathyroid hormone ( a clinically approved method for increasing osteoblast function) resulted in therapeutic benefit in three clinically relevant models of stem cell therapy. These results suggest that the niche may be a pharmacological target for altering stem cell function in settings of regenerative medicine.
引用
收藏
页码:96 / 99
页数:4
相关论文
共 29 条
[1]   Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor [J].
Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States ;
不详 ;
不详 ;
不详 ;
不详 ;
不详 .
Nature, 2006, 7076 (599-603) :599-603
[2]   Therapeutic targeting of a stem cell niche [J].
Adams, Gregor B. ;
Martin, Roderick P. ;
Alley, Ian R. ;
Chabner, Karissa T. ;
Cohen, Kenneth S. ;
Calvi, Laura M. ;
Kronenberg, Henry M. ;
Scadden, David T. .
NATURE BIOTECHNOLOGY, 2007, 25 (02) :238-243
[3]   Targeted therapy of multiple myeloma based upon tumor-microenvironmental interactions [J].
Anderson, Kenneth C. .
EXPERIMENTAL HEMATOLOGY, 2007, 35 (04) :155-162
[4]   Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche [J].
Arai, F ;
Hirao, A ;
Ohmura, M ;
Sato, H ;
Matsuoka, S ;
Takubo, K ;
Ito, K ;
Koh, GY ;
Suda, T .
CELL, 2004, 118 (02) :149-161
[5]   Parathyroid hormone-regulated production of stem cell factor in human osteoblasts and osteoblast-like cells [J].
Blair, HC ;
Julian, BA ;
Cao, X ;
Jordan, SE ;
Dong, SS .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 255 (03) :778-784
[6]   A perivascular niche for brain tumor stem cells [J].
Calabrese, Christopher ;
Poppleton, Helen ;
Kocak, Mehmet ;
Hogg, Twala L. ;
Fuller, Christine ;
Hamner, Blair ;
Oh, Eun Young ;
Gaber, M. Waleed ;
Finklestein, David ;
Allen, Meredith ;
Frank, Adrian ;
Bayazitov, Ildar T. ;
Zakharenko, Stanislav S. ;
Gajjar, Amar ;
Davidoff, Andrew ;
Gilbertson, Richard J. .
CANCER CELL, 2007, 11 (01) :69-82
[7]   Osteoblastic cells regulate the haematopoietic stem cell niche [J].
Calvi, LM ;
Adams, GB ;
Weibrecht, KW ;
Weber, JM ;
Olson, DP ;
Knight, MC ;
Martin, RP ;
Schipani, E ;
Divieti, P ;
Bringhurst, FR ;
Milner, LA ;
Kronenberg, HM ;
Scadden, DT .
NATURE, 2003, 425 (6960) :841-846
[8]   Inhibition of CD26 in human cord blood CD34+ cells enhances their engraftment of nonobese diabetic/severe combined immunodeficiency mice [J].
Campbell, Timothy B. ;
Hangoc, Giao ;
Liu, Ying ;
Pollok, Karen ;
Broxmeyer, Hal E. .
STEM CELLS AND DEVELOPMENT, 2007, 16 (03) :347-353
[9]   Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease [J].
Cavazzana-Calvo, M ;
Hacein-Bey, S ;
Basile, CD ;
Gross, F ;
Yvon, E ;
Nusbaum, P ;
Selz, F ;
Hue, C ;
Certain, S ;
Casanova, JL ;
Bousso, P ;
Le Deist, F ;
Fischer, A .
SCIENCE, 2000, 288 (5466) :669-672
[10]   Cancer stem cells: Models and concepts [J].
Dalerba, Piero ;
Cho, Robert W. ;
Clarke, Michael F. .
ANNUAL REVIEW OF MEDICINE, 2007, 58 :267-284