Treatment of streptozotocin-induced diabetes mellitus in rats by transplantation of islet cells from two major histocompatibility complex disparate rats in combination with intra bone marrow injection of allogeneic bone marrow cells.
BACKGROUND
We have established a new method for the transplantation of allogeneic pancreatic islets obtained from two different rat strains in combination with a newly developed bone marrow transplantation (BMT) method in which bone marrow cells (BMCs) are directly injected into the bone marrow cavity (intra bone marrow BMT [IBM-BMT]).


METHODS
Streptozotocin-induced diabetic Brown Norway (BN: RT1A(n)) rats were injected with fludarabine, irradiated with 5.0 Gy x 2, and BMCs from two allogeneic rat strains, Fischer 344 (F344: RT1A(1)) and PVG (PVG: RT1A(c)), were then directly injected into the bone marrow cavity (IBM-BMT). Simultaneously, approximately 600 pancreatic islets (PIs) from F344 and PVG rats were mixed and transplanted into the liver by way of the portal vein.


RESULTS
All the recipients thus treated showed normoglycemia 30 days after the treatment. Hematolymphoid cells were completely reconstituted with the two donor-type cells, and immunologic tolerance to F344 and PVG major histocompatibility complex (MHC) determinants were induced.


CONCLUSIONS
The transplantation of PIs from two MHC-disparate donors was completely achieved in combination with IBM-BMT, resulting in the improvement of blood glucose levels and the amelioration of diabetes mellitus.
Taira
Mitsuru
M
First Department of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan.
Inaba
Muneo
M
Takada
Keizo
K
Baba
Susumu
S
Fukui
Junichi
J
Ueda
Yusuke
Y
Kwon
A-Hon
AH
Hisha
Hiroko
H
Kamiyama
Yasuo
Y
Ikehara
Susumu
S
D000818:Animals; D000941:Antigens / Q000276:immunology; D001786:Blood Glucose / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D005951:Glucose Tolerance Test; D006085:Graft Survival / Q000276:immunology; D006648:Histocompatibility / Q000276:immunology*; D007515:Islets of Langerhans / Q000473:pathology; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D051381:Rats; D013311:Streptozocin / Q000494:pharmacology*; D013997:Time Factors; D014019:Tissue Donors; D018183:Transplantation Chimera / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology
D000941:Antigens; D001786:Blood Glucose; D013311:Streptozocin