Stem cell engraftment strategies.
The donor stem cell phenotype and host microenvironment determine the outcome of a stem cell transplant. In a series of transplant studies in syngeneic male to female or congenic Ly5.1/Ly5.2 models in which hosts have received no or minimal irradiation (100 cGy), evidence overwhelmingly supports the concept that syngeneic engraftment is determined by stem cell competition. These approaches can be extended to H-2 mismatched allogeneic mouse combination when antigen pre-exposure and CD40-CD40 ligand antibody blockage are employed. A human trial in patients with resistant neoplasia infusing pheresed blood with 10(8) CD3 cells/kg showed that tumor responses and complete chimerism occur with very low levels of CD34+ cells/kg and that the extent of previous treatment is a critical factor in determining chimerism. A major feature of transplants is the phenotype of the donor stem cell. This phenotype shows dramatic reversible plasticity involving differentiation, adhesion protein expression, and engraftment with cytokine-induced cell-cycle transit. Homing is probably also plastic. Marked fluctuations in engraftment capacity are also seen at different points in marrow circadian rhythm.
Quesenberry
P J
PJ
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Stewart
F M
FM
Becker
P
P
D'Hondt
L
L
Frimberger
A
A
Lambert
J F
JF
Colvin
G A
GA
Miller
C
C
Heyes
C
C
Abedi
M
M
Dooner
M
M
Carlson
J
J
Reilly
J
J
McAuliffe
C
C
Stencel
K
K
Ballen
K
K
Emmons
R
R
Doyle
P
P
Zhong
S
S
Wang
H
H
Habibian
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000950:Antigens, Ly / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000187:drug effects / Q000502:physiology; D019070:Cell Lineage; D002678:Chimera; D002940:Circadian Rhythm; D002986:Clinical Trials as Topic; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006082:Graft Enhancement, Immunologic / Q000379:methods; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease; D006183:H-2 Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D006648:Histocompatibility; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy; D010641:Phenotype; D011828:Radiation Chimera; D013154:Spleen / Q000166:cytology; D013789:Thalassemia / Q000628:therapy; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014916:Whole-Body Irradiation
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D019013:CD40 Antigens; D006183:H-2 Antigens; D023201:CD40 Ligand; D005472:Fluorouracil