Methods of treatment of hematopoietic disorders
A composition comprising bone marrow cells (BMC) and demineralized bone matrix (DBM) and/or mineralized bone matrix (MBM), optionally comprising bone morphogenetic protein (BMP), particularly for use in bone marrow transplantation, into bone marrow cavity or into extraskeletal sites, and methods of transplantation/implantation thereof. The composition and methods of the invention enable restoring and/or enhancing the formation of hematopoiectic microenvironment originating from the transplanted BMC, and are useful in the treatment of hematopoietic disorders, such as deficiency of stem cells and/or their products, genetic conditions resulting in abnormal stem cells and/or products, or hematopoietic disorders of malignant or non-malignant origin. The composition and method of the invention may also be used for the induction of graft tolerence, for the prevention of graft-v-host disease. It is mostly important that the compositions and methods of the invention may be applied for the treatment of diseases affecting primarily or secondarily the stromal microenvironment that supports and regulates hematopoiesis. Further provided is a kit for transplantation into a mammal of BMC in admixture with DBM and/or MBM.
1. A method of treating a mammal suffering from a hematopoietic disorder wherein bone marrow transplantation is required comprising administering into a bone marrow cavity or extra-skeletal site of the said mammal a mixture of bone marrow cells (BMC) and demineralized bone matrix (DBM) and/or mineralized bone matrix (MBM), said mixture optionally further comprising a pharmaceutically acceptable carrier and/or diluent.
2. The method according to claim 1 , wherein said mixture optionally further comprises a bone morphogenic protein (BMP).
3. The method according to claim 1 , further comprising administering to said mammal a stem cell suspension.
4. The method according to claim 1 , wherein the bone marrow cells (BMC) are allogeneic or said mammal's own.
5. A kit for transplantation into a mammal of bone marrow cells (BMC) in admixture with demineralized bone matrix (DBM) and/or mineralized bone matrix (MBM), wherein said mammal suffers from a hematopoietic disorder wherein bone marrow transplantation is required, said kit comprising:
a. DBM and/or MBM in a compacted form;
b. a BM aspiration needle
c. an intra-osseous bone drilling burr;
d. a needle with a thick lumen for infusion of viscous bone marrow-DBM or bone-marrow-MBM mixture;
e. a two-way lumen connector for simultaneous mixing of BMC-DBM or BMC-MBM with the diluent
f. a medium for maintaining BMC; and optionally
g. cryogenic means for handling and maintaining BMC or BMC together with DBM.
6. The method according to claim 3 , wherein said administration is by intravenous infusion.
7. The method of claim 1 wherein said hematopoietic disorder is selected from a deficiency of stem cells and/or their products, an abnormality of stem cells and/or their products, a genetic or acquired condition which results in abnormal stem cells and/or products and a hematopoietic disorder of malignant origin.
8. The method of claim 1 wherein said hematopoietic disorder affects stromal microenvironment that supports and regulates hematopoiesis.