SBIR Phase I: Development of a closed system for autologous cell therapy

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) project will be to transform the current models for bone marrow- and cord blood-derived cell therapies and make cell therapy, especially the patients' own cells, more widely available for use by healthcare providers and patients. Two major technical hurdles in the regenerative medicine field have prevented the translation of cell therapy from the bench to the bedside, despite the huge surge in clinical trials being conducted worldwide: 1) The lack of devices for the isolation of native clinically active bone marrow or cord blood derived cells without gradient selection and centrifugation that lead to cell loss and decreased cell viability; and 2) The logistical hurdles of cell isolation and processing in "centralized" cell production facilities. The prevalent approaches involve the collection of patient tissues such as bone marrow samples at hospitals, transport of samples to the central cell production facilities, isolation and expansion of cells using different protocols, and transporting the cell product back to the hospital sites for transplantation into patients. Every step of this cell therapy and transplantation process is expensive, involves multiple teams and poses a potential risk for introducing contamination, cellular loss and other complications. The technology proposed in this project is incorporated in a device that has the potential to overcome these two hurdles. The device allows the derivation of adherent bone marrow cells (ABMCs) that are native or minimally manipulated, in a GMP-compliant process for isolation and delivery of cells for cell therapy applications in hospitals and outpatient clinics, thereby circumventing transportation requirement and central facility processing and making cell therapy more widely available. This STTR Phase I project proposes to overcome the hurdles in the regenerative medicine field by developing a device that enables GMP-grade stem cell processing in a functionally closed system. This project will validate GMP-grade isolation of the fraction of the bone marrow, the adherent bone marrow cells (ABMCs) for use in cell therapy applications, initially for spinal cord injuries. While the ultimate goal is to conduct IND enabling studies, this Phase I grant objectives covers: 1) GMP-compliant coating of the device surface with matrix molecules and validation for efficient collection of ABMCs, 2) Post processing validation of ABMC sample integrity. Since the device also has a provision component for freezing of the processed samples, objective 3) is to validate ABMC freezing and cell recovery. Safety assays will include sterility and end product monitoring. Non-retrospective flow cytometry assays will be utilized to analyze CD34, CD44, CD45, CD73, CD90, CD105, CD106, CD166, and CD271 expression, essential markers that distinguish ABMCs. Higher percentages of CD106 and CD271 are expected for ABMCs. The potential for CFU-F formation, along with adipogenic, osteogenic and neuronal potentials of ABMCs will be examined and compared with standard mesenchymal stem cells. The collection of bone marrow cells with superior regenerative potentials, as indicated with previous pilot studies, is anticipated.