PMID- 21142526
OWN - NLM
STAT- MEDLINE
DCOM- 20120127
LR  - 20211020
IS  - 1557-8534 (Electronic)
IS  - 1547-3287 (Print)
IS  - 1547-3287 (Linking)
VI  - 20
IP  - 8
DP  - 2011 Aug
TI  - Mesenchymal stem cells secreting angiopoietin-like-5 support efficient expansion 
      of human hematopoietic stem cells without compromising their repopulating 
      potential.
PG  - 1371-81
LID - 10.1089/scd.2010.0456 [doi]
AB  - Clinical and preclinical applications of human hematopoietic stem cells (HSCs) 
      are often limited by scarcity of cells. Expanding human HSCs to increase their 
      numbers while maintaining their stem cell properties has therefore become an 
      important area of research. Here, we report a robust HSC coculture system wherein 
      cord blood CD34(+) CD133(+) cells were cocultured with mesenchymal stem cells 
      engineered to express angiopoietin-like-5 in a defined medium. After 11 days of 
      culture, SCID repopulating cells were expanded ~60-fold by limiting dilution 
      assay in NOD-scid Il2rg(-/-) (NSG) mice. The cultured CD34(+) CD133(+) cells had 
      similar engraftment potential to uncultured CD34(+) CD133(+) cells in competitive 
      repopulation assays and were capable of efficient secondary reconstitution. 
      Further, the expanded cells supported a robust multilineage reconstitution of 
      human blood cells in NSG recipient mice, including a more efficient T-cell 
      reconstitution. These results demonstrate that the expanded CD34(+) CD133(+) 
      cells maintain both short-term and long-term HSC activities. To our knowledge, 
      this ~60-fold expansion of SCID repopulating cells is the best expansion of human 
      HSCs reported to date. Further development of this coculture method for expanding 
      human HSCs for clinical and preclinical applications is therefore warranted.
FAU - Khoury, Maroun
AU  - Khoury M
AD  - Department of Biology, Koch Institute for Integrative Cancer Research, 
      Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
FAU - Drake, Adam
AU  - Drake A
FAU - Chen, Qingfeng
AU  - Chen Q
FAU - Dong, Di
AU  - Dong D
FAU - Leskov, Ilya
AU  - Leskov I
FAU - Fragoso, Maria F
AU  - Fragoso MF
FAU - Li, Yan
AU  - Li Y
FAU - Iliopoulou, Bettina P
AU  - Iliopoulou BP
FAU - Hwang, William
AU  - Hwang W
FAU - Lodish, Harvey F
AU  - Lodish HF
FAU - Chen, Jianzhu
AU  - Chen J
LA  - eng
GR  - T32 GM007753/GM/NIGMS NIH HHS/United States
GR  - DK067356/DK/NIDDK NIH HHS/United States
GR  - AI69208/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110131
PL  - United States
TA  - Stem Cells Dev
JT  - Stem cells and development
JID - 101197107
RN  - 0 (AC133 Antigen)
RN  - 0 (ANGPTL5 protein, human)
RN  - 0 (Angiopoietin-like Proteins)
RN  - 0 (Angiopoietins)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, CD34)
RN  - 0 (Glycoproteins)
RN  - 0 (PROM1 protein, human)
RN  - 0 (Peptides)
RN  - 0 (Prom1 protein, mouse)
SB  - IM
MH  - AC133 Antigen
MH  - Angiopoietin-like Proteins
MH  - Angiopoietins/*biosynthesis/genetics/metabolism
MH  - Animals
MH  - Antigens, CD/biosynthesis
MH  - Antigens, CD34/biosynthesis/blood
MH  - Cell Culture Techniques/methods
MH  - Cells, Cultured
MH  - Fetal Blood/cytology/transplantation
MH  - Glycoproteins/biosynthesis
MH  - Graft Survival/immunology
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Hematopoietic Stem Cells/*cytology/immunology/*metabolism
MH  - Humans
MH  - Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Mice
MH  - Peptides
MH  - T-Lymphocytes/transplantation
MH  - Transplantation, Heterologous/immunology
PMC - PMC3148832
EDAT- 2010/12/15 06:00
MHDA- 2012/01/28 06:00
PMCR- 2012/08/01
CRDT- 2010/12/15 06:00
PHST- 2010/12/15 06:00 [entrez]
PHST- 2010/12/15 06:00 [pubmed]
PHST- 2012/01/28 06:00 [medline]
PHST- 2012/08/01 00:00 [pmc-release]
AID - 10.1089/scd.2010.0456 [pii]
AID - 10.1089/scd.2010.0456 [doi]
PST - ppublish
SO  - Stem Cells Dev. 2011 Aug;20(8):1371-81. doi: 10.1089/scd.2010.0456. Epub 2011 Jan 
      31.