SBIR-STTR Award

Substitution of abnormal stem cells with healthy cells has been accomplished clinically through hematopoietic stem cell (HSC) transplantation for more than 50 years. Umbilical cord blood (UCB) is an alternative to bone marrow or peripheral blood HSC source for patients with hematologic diseases who need allogeneic hematopoietic cell transplantation. The first UCB transplantation was performed in 1988 for a child with Fanconi anemia. The field of UCB banking and transplantation has grown exponentially ever since. However, the number of banked UCB in both public and private banks is much lower than available umbilical cords. High costs and complex procedures are two major hurdles to be overcome. Recently, we have developed an innovative microbubble-based technology for rare cell isolation in blood that can help resolve these issues. We use perfluorocarbon-filled microbubbles (MBs), which have been used as a safe ultrasound contrast agent. Therefore, this material would be suitable for isolating cells for therapeutic applications. Here we propose to develop a close system that can be intuitively operated without the need of specialized equipment. By target isolation of HSC, this technology can reduce volume of a unit of cord blood (>20 ml) to be stored in a designed container with much small volume (< 1 ml). The simplicity of the procedure and reduction of the cost may revolutionize the UCB banking industry. In Phase 1, we will develop standardized methods for efficient HSC isolation using our proposed approach. In Phase 2, we will apply this established protocol to develop commercial products for clinical and research uses.

Public Health Relevance Statement:


Public Health Relevance:
The number of banked UCB in both public and private banks is much lower than available umbilical cords because of high costs and complex processing procedures. We have developed an innovative microbubble-based technology for rare cell isolation in blood that can help resolve these issues.

Project Terms:
Air; Allogenic; Anti-CEA Antibody; Bacteria; base; Biological; Blood; Blood Banks; Blood Circulation; Blood specimen; Blood Volume; Bone Marrow; Cancer Patient; Carbon; CD34 gene; cell bank; Cell Separation; Cell Therapy; Cells; Child; Clinical; clinical application; clinical Diagnosis; Clinical Research; Complex; Contrast Media; cost; cryogenics; design; Development; Device Designs; Devices; Drug Formulations; Engineering; Epidermal Growth Factor Receptor; Epithelial; Equipment; Fanconi's Anemia; Feasibility Studies; Fluorocarbons; Freezing; Growth; Harvest; Hematological Disease; Hematopoietic; hematopoietic cell transplantation; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Industry; innovation; innovative technologies; Laboratories; Lung; Malignant Neoplasms; Marketing; Methods; Microbubbles; microorganism; Mission; Modeling; Neoplasm Circulating Cells; Nucleic Acids; Parasites; Patients; peripheral blood; Phase; Procedures; Process; Property; Proteins; Protocols documentation; prototype; public health relevance; Recovery; Sampling; skills; Small Business Innovation Research Grant; Source; Staging; stem; stem cell technology; Stem cells; Syringes; System; TACSTD2 gene; Techniques; Technology; Therapeutic; Time; Transplantation; Tube; Ultrasonography; Umbilical Cord Blood; Umbilical Cord Blood Transplantation; Umbilical cord structure; Virus; Work

Umbilical cord blood (UCB) has been an alternative source for patients with hematologic diseases who may be potentially cured by allogeneic hematopoietic cell transplantation. In addition, UCB is an important stem cell source for other promising technologies, such as large-scale ex vivo productions of hematopoietic stem cell (HSC)-derived red blood cells and platelets. In the 25 years following the first successful case of transplantation in 1988, more than 30,000 UCB transplantations have been performed with > 600,000 UCB units stored worldwide. Initially, UCB transplantation was mainly performed in children, given the concern of low cell dose. As cell dose is critical for engraftment and survival, infusing two units of UCB has been a popular practice for adult patients. However, this approach makes HLA matching even more challenging. Remarkably, it has been estimated that current total UCB collections represent < 5% of potentially available cords. Therefore, there is an unmet need for innovative and low-cost solutions to increase the number and HLA diversity of banked UCB units, as well as to overcome the cell dose limitation of each UCB unit. Furthermore, an international survey conducted by the World Marrow Donor Association in 2013 revealed that nearly 90% of public UCB banks are not financially sustainable. Recently, we have developed an innovative microbubble- based technology for rare cell isolation in blood that can help resolve these issues. We use perfluorocarbon- filled microbubbles (MBs), which have been used as a safe ultrasound contrast agent, to create targeted agents for sorting. Therefore, this material would be suitable for isolating cells for therapeutic applications. We will create the targeted microbubble based system to isolate HSCs, which leads to substantial reduction of the final product volume (< 1 ml) compared to current standard unit (> 20 ml) for banking. This factor alone will lead to > 20-fold savings on long-term storage in liquid nitrogen. The simplicity of the procedure has been shown in publications, and reduction of the cost may revolutionize the UCB banking industry to facilitate realization of emerging innovations in cell based therapies, aside from more conventional hematopoietic cell transplantation. We have accomplished key feasibility milestones for the phase I grant and will develop a closed system to isolate HSCs from UCB for potential clinical applications, including hematopoietic transplantation and ex vivo blood production. Moreover, this system can also be conveniently adapted for HSC isolation from other sources, including peripheral blood and bone marrow.

Public Health Relevance Statement:
Project Narrative The number of banked UCB in both public and private banks is much lower than available umbilical cords because of high costs and complex processing procedures. We have developed an innovative microbubble-based technology for rare cell isolation in blood that can help resolve these issues.

Project Terms:
Adult; Air; Albumins; Allogenic; base; Biological Assay; Biological Models; Blood; Blood Banks; Blood Circulation; Blood Platelets; blood product; Bone Marrow; Carbon; CD34 gene; CD7 gene; Cell Separation; Cell Therapy; Cells; Child; Clinical; clinical application; Collection; Complex; Contrast Media; cost; cryogenics; Cryopreservation; design; Devices; Dose; Engineering; Engraftment; Equipment; Erythrocytes; Fluorescence-Activated Cell Sorting; Fluorocarbons; Formulation; Gases; Glass; Goals; Grant; Growth; Hematological Disease; Hematopoietic; hematopoietic cell transplantation; Hematopoietic stem cells; Immune; Industry; Injectable; innovation; International; intravenous injection; Lipids; Liquid substance; Lung; Magnetism; Marrow; Methods; Microbubbles; mouse model; Mus; Names; Neoplasm Circulating Cells; Nitrogen; Patients; peripheral blood; Phase; phase 1 study; physical property; portability; pre-clinical; Preparation; Privatization; Procedures; Process; Production; programs; Publications; Publishing; Recovery; Reporting; Research; Savings; scale up; skills; Sorting - Cell Movement; Source; Stem cells; Sterility; surface coating; Surveys; System; T cell differentiation; T-Cell Development; T-Lymphocyte; targeted agent; Techniques; Technology; Therapeutic; Transplantation; Tube; Ultrasonography; Umbilical Cord Blood; Umbilical Cord Blood Transplantation; Umbilical cord structure; Xenograft procedure