Blood Derived Mesenchymal Stem Cells Isolated With Use of FMB Grew and Differentiated
Ortec International, Inc. (OTC Bulletin Board:
ORTN -
News), a company focused on development and commercialization of products applicable to regenerative medicine and stem cell therapy, today announced the results of experiments showing the ability of Fibrin Microbeads (FMB), an advanced fibrin based biomaterial, to isolate the Mesenchymal class of adult stem cells (MSC) from human peripheral blood. The research has been published in the May issue of the journal, Bone Marrow Transplantation. The stem cells isolated by attachment to FMB were shown to be able to expand and differentiate into cartilage (chondrocytes), fat (adipocytes) and bone (osteoblasts) forming cells. This finding is unique, since it was previously thought that adult MSC were not found in blood in any significant quantity. The results using FMB demonstrate that blood may indeed prove to be a useful source of these stem cells for therapeutic applications. FMB is one of two proprietary fibrin derived advanced biomaterial technologies recently acquired by Ortec.
Ron Lipstein, Vice Chairman and CEO of Ortec, commenting on the published results, said, "These experiments demonstrate that, contrary to the skepticism in the current scientific literature, FMB allow blood to be used as a source of all types of adult stem cells. Providing the capability to source mesenchymal stem cells from blood would obviate the need to rely solely on the more invasive and less available bone marrow or fat. The ability of FMB to isolate adult stem cells beyond the hematopoietic type is a unique and significant development in stem cell therapy. During the coming year we will look to broaden the significance and application of this unique aspect of the FMB technology."
Melvin Silberklang, Ph.D., Chief Scientific Officer of Ortec, added that, "These results highlight the unique ability of FMB to efficiently recover the mesenchymal type of stem cells from the most readily available body tissue, blood. This capability may make autologous stem cell therapy for tissue or organ regeneration as accessible as many other blood-based separation technologies that are available today."
The experiments, which were the basis of the published article, were conducted at Hadassah Hebrew University Medical Center, Jerusalem Israel. In these experiments FMB were used to isolate non-hematopoietic stem cells from mobilized peripheral blood of adult donors treated with granulate colony- stimulating factor (GCSF). Attempts to isolate these stem cells by standard isolation methods resulted in recovery of a negligible number of MSC in all blood samples tested. In contrast, the substantial number of such cells isolated using FMB stained positive for mesenchymal stem cell markers, expressed vimentin and fibronectin and were negative for hematopoietic markers. They were also able to expand on the FMB or on plastic in eight out of the eleven samples tested.
Previously published results showed the ability of FMB to isolate and expand mesenchymal adult stem cells from mouse and rat bone marrow at a yield which is 3 to 5 times that of conventional isolation techniques, and showed that those isolated cells were able to form bone structures both in vitro and in vivo.
About Ortec International, Inc.
Ortec International, Inc. (ORTN) is a company focused on advancing regenerative medicine and stem cell therapy through the development and commercialization of innovative products by combining advanced cell technology and advanced biomaterials. Ortec's lead product is OrCel® (Bilayered Cellular Matrix). Ortec's current focus is the application of OrCel® to heal chronic and acute wounds. OrCel® is composed of a collagen sponge seeded with allogeneic epidermal and dermal cells. These cells secrete growth factors and cytokines normally found in acute human wounds and are believed to have a beneficial role in promoting tissue repair.
A pivotal clinical trial evaluating a cryopreserved version of OrCel® in the treatment of venous leg ulcers has been completed and a Pre Market Approval (PMA) application has been filed. Ortec has recently completed patient enrollment in a confirmatory trial and the data from this trial are expected to be integrated with the results of the pivotal clinical trial and submitted as a clinical supplement to its PMA filing. Ortec has already obtained FDA approvals for use of a non-frozen version of OrCel® in the treatment of Epidermolysis Bullosa and donor sites in burn patients. In addition, the FDA has granted Ortec approval to initiate a pivotal (Phase III) trial evaluating OrCel® for the treatment of diabetic foot ulcers.
Ortec recently acquired two fibrin derived advanced biomaterial technologies, Fibrin Microbeads (FMB) and Haptides(TM). FMB have the potential to play a significant role in advancing stem cell therapy having demonstrated the ability to efficiently recover adult stem cells and allow for their growth, proliferation, and potential reimplantation into the patient. Haptides(TM) utilize proprietary synthetic peptides that mimic the mechanism of cell attachment to fibrin. These peptides have demonstrated the ability to significantly enhance cell attraction and attachment providing the potential to use Haptides(TM) in the development of product opportunities applicable to the cosmetic tissue augmentation, wound healing, orthopedics, and drug delivery markets
Kassis I et al. Isolation of mesenchymal stem cells from G-CSF-mobilized human peripheral blood using fibrin microbeads. Bone Marrow Transplant. 2006 May;37(10):967-76
1Radiobiology and Biotechnology Laboratory, Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Adult mesenchymal stem cells (MSC) that are able to differentiate into various mesenchymal cell types are typically isolated from bone marrow, but their significant presence in human peripheral blood (PB) is controversial. Fibrin microbeads (FMB) that bind matrix-dependent cells were used to isolate MSC from the mononuclear fraction of mobilized PB of adult healthy human donors treated with a granulocyte colony-stimulating factor. Isolation by plastic adherence resulted in a negligible number of MSC in all samples tested, whereas FMB-based isolation yielded spindle-shaped cell samples that could further expand on plastic or on FMB in eight out of the 11 samples. The yield of these cells at days 17-18 after the harvest was approximately 0.5% of the initial cell number. The isolated cells were grown on plastic and characterized by FACS analysis and immunohistochemistry for specific markers. Following culturing and first passage, the FMB-isolated cells stained positive for mesenchymal stromal cell markers CD90 and CD105, expressed vimentin and fibronectin and were negative for hematopoietic markers CD45 and CD34. These cells could differentiate into osteoblasts, adipocytes and chondrocytes. This study indicates that FMB may have special advantage in isolating MSC from sources such as mobilized PB, where the number of such cells is scarce. Bone Marrow Transplantation (2006) 37, 967-976. doi:10.1038/sj.bmt.1705358.
