PMID- 12962730
OWN - NLM
STAT- MEDLINE
DCOM- 20031021
LR  - 20191026
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 31
IP  - 9
DP  - 2003 Sep
TI  - Stem cell activity of porcine c-kit+ hematopoietic cells.
PG  - 833-40
AB  - OBJECTIVE: A marker for hematopoietic stem cells (HSCs) of pigs, which are 
      considered to be the most suitable donors for clinical xenotransplantation, has 
      not yet been identified. In this study, we examined the HSC activity of porcine 
      c-kit+ bone marrow cells (BMCs). METHODS: The HSC activity of porcine c-kit+ BMCs 
      was evaluated both in vitro using colony-forming unit (CFU) and cobblestone 
      area-forming cell (CAFC) assays and in vivo in nonobese diabetic/severe combined 
      immunodeficiency transgenic (NOD/SCID-Tg) mice carrying porcine cytokine 
      transgenes. RESULTS: Purified c-kit+ BMCs were substantially enriched for both 
      CFUs and CAFCs in vitro and their transplantation led to long-term porcine 
      hematopoiesis in vivo in mice. Although porcine chimerism was detectable in the 
      peripheral blood of NOD/SCID-Tg mice receiving porcine c-kit- BMCs at early time 
      points after transplantation, the levels were markedly lower than those in mice 
      receiving purified c-kit+ BMCs (0.2%+/-0.14% vs 7.7%+/-1.6% and 0.17%+/-0.17% vs 
      5.6%+/-2.1% at weeks 3 and 6, respectively). Importantly, all mouse recipients of 
      porcine c-kit+ BMCs showed durable multilineage chimerism (>19 weeks), whereas no 
      recipients of porcine c-kit- BMCs sustained long-term engraftment. Moreover, 
      porcine HSCs that had engrafted for 19 weeks in the recipients of porcine c-kit+ 
      BMCs gave rise to clonogenic progenitors in vitro and reconstituted porcine 
      hematopoiesis in secondary recipients. CONCLUSION: The present study demonstrates 
      that c-kit is an essential marker of both long-term-repopulating HSCs and 
      progenitor cells with early engraftment capacity.
FAU - Le Guern, Annie C
AU  - Le Guern AC
AD  - BioTransplant, Incorporated, Charlestown, Mass., USA.
FAU - Giovino, Maria A
AU  - Giovino MA
FAU - Abe, Masahiro
AU  - Abe M
FAU - Theodore, Pierre R
AU  - Theodore PR
FAU - Qi, Jin
AU  - Qi J
FAU - Down, Julian D
AU  - Down JD
FAU - Sachs, David H
AU  - Sachs DH
FAU - Sykes, Megan
AU  - Sykes M
FAU - Yang, Yong-Guang
AU  - Yang YG
LA  - eng
GR  - P01 HL18646/HL/NHLBI NIH HHS/United States
GR  - R01 HL54038/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
SB  - IM
MH  - Animals
MH  - *Bone Marrow Cells/cytology/physiology
MH  - Colony-Forming Units Assay
MH  - Graft Survival
MH  - *Hematopoietic Stem Cells/cytology/physiology
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Proto-Oncogene Proteins c-kit/physiology
MH  - Stem Cell Transplantation
MH  - Swine
MH  - Transplantation, Heterologous
EDAT- 2003/09/10 05:00
MHDA- 2003/10/22 05:00
CRDT- 2003/09/10 05:00
PHST- 2003/09/10 05:00 [pubmed]
PHST- 2003/10/22 05:00 [medline]
PHST- 2003/09/10 05:00 [entrez]
AID - S0301472X03001978 [pii]
AID - 10.1016/s0301-472x(03)00197-8 [doi]
PST - ppublish
SO  - Exp Hematol. 2003 Sep;31(9):833-40. doi: 10.1016/s0301-472x(03)00197-8.