PMID- 16797423
OWN - NLM
STAT- MEDLINE
DCOM- 20060822
LR  - 20060626
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 34
IP  - 7
DP  - 2006 Jul
TI  - Rapid immune reconstitution and dendritic cell engraftment post-bone marrow 
      transplantation with heterogeneous progenitors and GM-CSF treatment.
PG  - 951-64
AB  - OBJECTIVE: Bone marrow/hematopoietic stem cell transplantation (BMT) has been the 
      treatment of choice for severe hematological diseases and cancers. Rapid host 
      immune recovery following BMT is critical for reducing complications and 
      improving therapeutic outcome. Here we report manipulations that facilitate rapid 
      immune and dendritic cell (DC) reconstitution post-BMT for improvement in 
      therapeutic outcome of BMT-based disease treatment. METHODS: Using lentiviral 
      vector-modified or unmodified murine hematopoietic stem cells, we examined the 
      engraftment efficiency and kinetics in immune reconstitution of unfractionated 
      bone marrow cells (BM), lineage marker-negative (Lin-) hematopoietic progenitor 
      cells (HPC), or purified Lin-Sca-1+ hematopoietic stem cells (HSC) at an equal 
      hematopoietic progenitor number. RESULTS: Our study revealed that BM 
      reconstituted host primary and secondary lymphoid tissues more efficiently and 
      rapidly. Moreover, in a competitive BMT setting using lentiviral 
      vector-engineered BM and HSC expressing GFP or DsRed respectively, we showed that 
      GM-CSF treatment further enhanced DC reconstitution to therapeutic relevant level 
      as early as 2 weeks post-BMT. On the other hand, Flt3 ligand was less effective 
      in enhancing DC reconstitution till 3 weeks post-BMT. This accelerated DC 
      engraftment by GM-CSF treatment correlated well with improved overall immune 
      reconstitution and enhanced activation of antigen-specific T cells post-BMT. 
      CONCLUSION: This study suggests that use of heterogeneous BM for transplantation 
      facilitates more rapid immune reconstitution, especially in the presence of 
      DC-stimulating cytokines. This improved immune reconstitution would provide 
      additional therapeutic benefits for BMT-based immunotherapy and gene therapy of 
      genetic disorders and cancers.
FAU - Zhao, Peilin
AU  - Zhao P
AD  - Gene Therapy Program, Departments of Medicine and Genetics, Louisiana State 
      University Health Sciences Center, New Orleans, LA 70112, USA.
FAU - Liu, Wei
AU  - Liu W
FAU - Cui, Yan
AU  - Cui Y
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - *Bone Marrow Transplantation
MH  - Dendritic Cells/*cytology
MH  - Flow Cytometry
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/*administration & dosage
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
EDAT- 2006/06/27 09:00
MHDA- 2006/08/23 09:00
CRDT- 2006/06/27 09:00
PHST- 2006/01/11 00:00 [received]
PHST- 2006/03/21 00:00 [revised]
PHST- 2006/04/10 00:00 [accepted]
PHST- 2006/06/27 09:00 [pubmed]
PHST- 2006/08/23 09:00 [medline]
PHST- 2006/06/27 09:00 [entrez]
AID - S0301-472X(06)00264-5 [pii]
AID - 10.1016/j.exphem.2006.04.015 [doi]
PST - ppublish
SO  - Exp Hematol. 2006 Jul;34(7):951-64. doi: 10.1016/j.exphem.2006.04.015.