PMID- 17960668
OWN - NLM
STAT- MEDLINE
DCOM- 20071026
LR  - 20191026
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 35
IP  - 6
DP  - 2007 Jun
TI  - Formation of hematopoietic territories and bone by transplanted human bone marrow 
      stromal cells requires a critical cell density.
PG  - 995-1004
AB  - OBJECTIVE: Bone marrow stromal cells (BMSCs) include multipotent cells with the 
      ability to form mature bone organs upon in vivo transplantation. Hematopoiesis in 
      these bone organs has been ascribed to the action of skeletal stem cells, which 
      are capable of differentiating towards bone and hematopoiesis-supporting stroma. 
      Yet, the creation of hematopoietic territories may be in part a natural 
      consequence of the formation of a sufficiently mature and large bone 
      microenvironment. Here, we describe, for the first time, a relationship between 
      BMSC numbers and the extent of bone/hematopoiesis formation in heterotopic 
      transplants. METHODS: Human BMSCs were transplanted along with 
      hydroxyapatite/tricalcium phosphate, utilizing a spectrum of dosages, into 
      immunotolerant mice; the transplants were followed for up to 29 months. RESULTS: 
      The extent of bone and hematopoiesis formation increased with increasing BMSC 
      numbers; however, the relationship was sigmoid in character, and a threshold 
      number of BMSCs was necessary for extensive bone formation or any hematopoiesis. 
      Hematopoiesis only occurred in conjunction with extensive bone formation, and no 
      hematopoiesis occurred where bone formation was poor. Consistent with our earlier 
      studies of long-term BMSC transplantation, the transplants underwent a change in 
      bone morphology but not bone content after 8 weeks. CONCLUSION: Our results have 
      provided evidence that the formation of both hematopoiesis and a mature bone 
      organ is as much a consequence of a sufficiently high local density of bone 
      marrow stromal cells as it is the product of skeletal stem cell action.
FAU - Mankani, Mahesh H
AU  - Mankani MH
AD  - Division of Plastic Surgery, Department of Surgery, University of California-San 
      Francisco, San Francisco, Calif., USA. mahesh.mankani@ucsf.edu
FAU - Kuznetsov, Sergei A
AU  - Kuznetsov SA
FAU - Robey, Pamela Gehron
AU  - Robey PG
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
SB  - IM
MH  - Adolescent
MH  - Animals
MH  - *Bone Marrow Cells
MH  - Cell Count
MH  - Cell Differentiation
MH  - Cell Transplantation
MH  - Female
MH  - *Hematopoiesis
MH  - Humans
MH  - Immunocompromised Host
MH  - Male
MH  - Mice
MH  - *Osteogenesis
MH  - Stem Cells/cytology
MH  - *Stromal Cells/cytology/transplantation
MH  - Tissue Engineering
MH  - *Transplantation, Heterotopic
EDAT- 2007/10/26 09:00
MHDA- 2007/10/30 09:00
CRDT- 2007/10/26 09:00
PHST- 2007/10/26 09:00 [pubmed]
PHST- 2007/10/30 09:00 [medline]
PHST- 2007/10/26 09:00 [entrez]
AID - S0301-472X(07)00063-X [pii]
AID - 10.1016/j.exphem.2007.01.051 [doi]
PST - ppublish
SO  - Exp Hematol. 2007 Jun;35(6):995-1004. doi: 10.1016/j.exphem.2007.01.051.