The National Center for Regenerative Medicine (NCRM) is a platform to facilitate translational research, clinical application, and commercialization of regenerative medicine, tissue engineering, and stem cell therapeutics across a consortium of institutions. NCRM is driven by three nationally ranked medical research powerhouses—Case Western Reserve University, Cleveland Clinic, MetroHealth Medical Center and University Hospitals. Through this network of researchers and clinicians, research discoveries are actively being translated into cell-based therapies for patient care.
NCRM is leading the way in Northeast Ohio in the following areas:
- Regenerative medicine and stem cell research
- Cellular manufacturing
- Clinical trials for cellular therapeutics
Global partnerships have been established with academic institutions and biotechnology companies to further expand research and discovery efforts.
Our Goals
- Translational Research: To support stem cell and regenerative medicine research across various disciplines, institutions, and commercial entities.
- Education and Training: To develop cutting-edge education programs for researchers, clinicians, trainees, and the general public.
- Strategic Partnership: To build networks across academic, clinical, commercial, and public sectors.
- Commercialization: To translate innovative technologies and cell-therapies into business opportunities.
Our History
The Center for Stem Cell and Regenerative Medicine (CSCRM) is a multi-institutional center comprised of investigators from Case Western Reserve University (CWRU), University Hospitals (UH), the Cleveland Clinic (CC), Athersys, Inc., and The Ohio State University (OSU). Building on the 30-year history of adult stem cell research in northeast Ohio, the Center was created in 2003 as a Wright Center of Innovation with a $19.4 million award from the State of Ohio. An additional $8 million was awarded in 2006 from the State of Ohio’s Biomedical Research and Commercialization Program--and, in June 2009, a $5 million award from Ohio’s Third Frontier Commission further validated NCRM’s ability to achieve its mission to utilize human stem cell and tissue engineering technologies to treat human disease. Subsequent projects supported spin-off companies such as Trailhead (CEO Jen Jenson), Arteriocyte, and the Cleveland Cord Blood Center. Arnold Caplan’s discoveries in Mesenchymal Stem Cells benefited NCRM immensely and led to the CWRU spin off, Osirus, that merged with Mesoblast.
Senator George Voinovich, with strong support of Ohio Congressman Ralph Regula, provided over $7.7M to establish Cleveland’s National Center for Regenerative Medicine in April 2007. A visit from Voinovich and Regula resulted in the construction of the Lerner Research Institute Department of Stem Cell Biology, the research cell therapy patient beds in the new Seidman Cancer Center, and the cell production facility in the Wolstein Research Building. A record of Senator Voinovich’s speech can be found in the Congressional Record, April 7, 2007, S4350-S4351.
Representing a new paradigm in biomedical research and therapy, regenerative medicine uses stem cells to regenerate new tissue within diseased organs rather than using drugs or devices to improve their function. NCRM provides a comprehensive and coordinated “bench to bedside” approach to regenerative medicine, including basic and clinical research programs, and biomedical and tissue engineering programs, and develops and administers new therapies to patients. Leveraging its investigators’ exceptional track records in stem cell, tissue engineering, and “first-in-the-nation” stem cell clinical trials, the NCRM promotes cutting-edge research that is translated into clinical and commercial applications. It builds on existing excellence in heart disease, adult stem cell transplantation, cancer, genetic disorders, and musculoskeletal and neurodegenerative diseases such as multiple sclerosis at the affiliated institutions. The first five worldwide clinical trials using Mesenchymal Stem Cells were NCRM-based and conducted by Hillard Lazarus, Omer Koc, and Jeffery Cohen.
Established investigators with proven expertise in stem cell research and clinical studies from the five institutions have come together to bring an impressive breadth of skills and experience to NCRM. The extensive scope of adult and pluripotent stem cell types under study at NCRM is comprised of ASC (adipose stem cells), CSC (cochlear stem cells), CTP (connective tissue progenitors), ESC (embryonic stem cells), HSC(hematopoietic stem cells), HB1 (hemangioblast AC133+ cells from umbilical cord blood), iPS (induced pluripotent stem cells), MSC (mesenchymal stem cells), MAPC (multi-potent adult progenitor cells), NSC(neural stem cells/oligodendrocyte progenitors), SKMB (skeletal myoblasts), and UCB (umbilical cord blood-derived stem cells). They are being investigated for therapeutic uses in cancer, musculoskeletal, orthopedic, cardiovascular, hematopoietic and neurodegenerative disorders.
The Reshmi Parameswaran Lab focuses on developing new cellular therapy approaches for treating various malignancies, including liquid and solid tumors, and autoimmune diseases. Parameswaran’s lab recently developed BAFF ligand-based CAR-T therapy targeting three receptors simultaneously (3-in-1 CAR) and published a patent. BAFF CAR-T has shown therapeutic efficacy in various B cell cancer mouse models (published in Nature Communications 2022) and entered clinical trials for Non-Hodgkin Lymphoma and Multiple Myeloma. A phase 1 trial, licensed and supported by Luminary, is now active at UH and CC. BAFF CAR-T also received IND approval for treating autoimmune lupus patients and the clinical trial is expected to initiate soon. The lab submitted another patent for a new CAR design optimized for Natural Killer (NK) cells suitable for any tumor-specific target and generated BAFF CAR-NK cells as a potential “off-the-shelf” therapy using Dr. Ralph and Marian Falk Medical Research Trust Award ($1.3M) to develop this technology. Parameswaran Lab researchers are performing pre-clinical IND-enabling studies using BAFF CAR-NK cells for B cell cancers and autoimmune diseases with autoreactive B cell involvement including lupus, scleroderma, type-1 diabetes, and rheumatoid arthritis. Another CAR recently developed in the Parameswaran Lab, Oncostatin-M (OSM), targets receptors of OSM. It shows significant tumor-killing efficacy in pre-clinical mouse models against many solid tumors including osteosarcoma and triple-negative breast cancer.
The David Wald Lab has extensively worked with NCRM to develop novel manufacturing strategies for adoptive cellular therapies and to translate new products to the clinic. For example, a new ex vivo expansion platform for NK cells was developed to enable the production of large numbers of highly cytotoxic “universal donor” off-the-shelf NK cells. Clinical testing with this product demonstrated the safety and promise for the first time of fully HLA mismatched, adoptively infused peripheral blood-derived NK cells. The Lab also focuses on the creation of an ultra-fast CAR-T manufacturing workflow that enables the production of CAR-T products in less than one day. This manufacturing approach helps to overcome accessibility hurdles, such as high costs and long delays to treatment, inherent with the FDA-approved CAR-T products. Additionally, as the manufacturing preserves naive/early memory T cells, this approach is predicted to increase efficacy and reduce the side effects of CAR-T products. A recently complete Phase I clinical trial for a patient with lymphoma supports its promise. Not only were the side effects limited, but there was an 80% complete remission rate. As the initial patient was treated over 18 months ago and all responding patients remain in remission to date, the therapy has shown high durability compared to the FDA-approved products that have high relapse rates in the first year after treatment.
NCRM continues to focus on the versatile and powerful capacity of MSCs to provide either structural- or cell-based therapy for diseases. The Bonfield Lab partners with Dr. Arnold Caplan to pursue MSC development for treating steroid-resistant asthma and the co-morbid infection and inflammation of cystic fibrosis (CF). The powerhouse of MSC biology has to do with its site-specific delivery capacity of bio-active factors that has a direct impact on tissue inflammation and infection while enhancing the recipient’s capacity to self-heal. These studies resulted in the “First in CF” MSC Phase I clinical trial with Drs. James Chmiel, Erica Roesch and Hillard Lazarus at UH’s Rainbow Babies & Children’s Hospital. The completed clinical trial demonstrated safety and has provided the fuel for collaborations to harness MSCs for their potential to provide clinical benefit throughout the CF research community. The capacity for MSCs to respond to their environment adds the advantage of defining what factors are produced and when. The maturity of the science behind MSC biology has evolved toward implementing potency assays along with the MSC’s molecular fingerprint to streamline clinical products for good manufacturing procedures and clinical translation. In the CF space, Dr. Bonfield, along with NCRM, is moving toward a Phase II multi-centered global clinical trial focusing on non-tuberculous mycobacterium pulmonary diseases in CF. The efficiency MSC potency assays and facilitating MSC clinical initiatives have included other NCRM collaborations between UH, MetroHealth Medical Center, and CC. The capacity of MSCs to provide structural foundations for tissues continues, in partnership with the Skeletal Research Center (Founded by Dr. Arnold Caplan) in the School of Arts and Sciences with Mechanical and Aerospace Engineering and the Musculoskeletal Material and Mechanics group as part of the ARPA-H funded multi-institutional OMEGA project centered at CWRU.
CC is an integral partner of the NCRM, having worked on many initiatives. Dr. Timothy Chan moved to Cleveland in 2020 and founded the Global Center for Immunotherapy and Precision Immuno-Oncology (CITI). One of CITIs areas of focus is to work with the NCRM to develop new CART agents and new process development capabilities. Heading this effort in CITI, Dr. Jan Joseph Melenhorst has developed next- generation CARTs against B7H3 and other targets. Dr. Melenhorst is starting a clinical trial with this new CART. Aside from CART development, CC investigators have worked with the NCRM to produce and test mesenchymal stem cells in a number of clinical trials for inflammatory disorders. Dr. Chan’s team has built state-of-the-art immunomonitoring and genomics capabilities for NCRM investigators to maximize generation of correlative data from NCRM trials. Dr. Chan and Dr. Melenhorst also are working to build additional GMP expansion space for the NCRM community focusing on nanoparticle and vaccine production capabilities, with ground-breaking happening in early 2025.