Department of Surgery
Islet cell transplantation is the most potent therapy for patients with type 1 diabetes. However, there are two major problems besetting this process. First, there are not enough islets available for transplant. Second, islets after transplantation are often undergoing apoptosis due to the stresses encountered during islet harvest and after transplantation. The ongoing projects in the Islet Cell Transplantation lab led by Dr. Hongjun Wang are focused on pancreatic islet cell biology and transplantation immunology in the treatment of type 1 and type 2 diabetes and chronic pancreatitis. The primary areas of investigation in the Wang lab include:
- Generation of insulin-secreting cells from adipose stem cells to expand the source of transplanted islets
- Mechanisms that lead to islet death after allogeneic and autologous islet transplantation
- Interventional approaches that can protect islets from apoptosis and immune rejection by induction of protective genes or encapsulating islets with nanoparticles
- The role of HO-1 in obesity and insulin resistance
- A translational approach that can prevent the onset of surgical diabetes after total pancreatectomy and islet autotransplantation for patients with chronic pancreatitis.
Type 1 Diabetes
Islet cell transplantation is the most potent therapy for patients with type 1 diabetes. However, there are two major problems besetting this process. First, there are not enough islets available for
transplant. Second, islets after transplantation are often undergoing apoptosis due to the stresses encountered during islet harvest and after transplantation and the consequent immune rejection response, thus their function is compromised. Ongoing projects in the Wang lab focus on solving these problems. Major areas of investigation include:
- The roles of a protective gene, heme oxygenase-1 (HO-1) and its products, carbon monoxide and bilirubin in islet transplantation;
- Generation of insulin-secreting cells from adult stem cells (e.g., adipose stem cells, umbilical cord stem cells) to expand source of transplanted islets;
- Developing novel encapsulation methods using FDA approved nanoparticles to protect islets from apoptosis and immune rejection;
- Understanding the role of the Regulator of G Protein Signaling 2 (RGS2) in islet regeneration.
Chronic Pancreatitis (CP)
CP is a long-standing inflammation of the pancreas that alters its normal structure and functions. Current therapies for CP patients focus on pain relief medically, endoscopically and surgically (by resection of diseased parenchyma and drainage of obstructed ducts). In patients with intractable pain and those with diffuse small duct diseases, total pancreatectomy with islet autotransplantation (TP-IAT) can be an ideal treatment option. Together with Drs. David B Adams and Katherine A Morgan, we are developing interventional procedures including induction of protective genes, nano-encapsulation, and cotransplantation with mesenchymal stem cells to improve islet yield quantity and quality in order to prevent onset of surgical diabetes after TP-IAT in patients with chronic pancreatitis. These are all areas that a bioengineered approach may help facilitate clinical translational science.
Clean Cell Facility for Tissue Engineering
The second floor of the Clinical Science Building at MUSC houses The Center for Cellular Therapy (CCT). The primary goals of the CCT are to: produce expanded celltherapy and gene-therapy based biotherapeutic products for Phase I and II clinical studies (employing current Good Manufacturing Practices (cGMP)), serve as a regulatory resource to MUSC in the preparation of cell and gene-therapy based INDs, and to facilitate clinical development of novel cellular cancer therapies. The CCT facility houses three fully equipped, FDA/ISO compliant, manufacturing suites available for clinical trials using cell-mediated therapy. The CCT facility consists of three components: a 200 sq. ft. Process Optimization Lab, a 200 sq. ft. Materials Management/QC Laboratory, and a 1000 sq. ft. clean room suite comprised of manufacturing rooms, general processing area, storage, gowning and de-gowning areas. The cGMP clean room suite contains three annually certified ISO 14644-1 compliant Class 6 manufacturing rooms, with monthly in-house testing placing them at or below Class 5. Each of these is a fully functional processing laboratory containing well-maintained, highest quality laboratory equipment. In addition, each room contains at least one Class 5 Biological Safety Cabinet (BSC) for performing open system sterile processing. The CCT staff has extensive experience in all aspects of cellular therapy and cGMP Phase I/II manufacturing of autologous cellular products. This includes cGMP handling of blood components; dendritic cell, T cell & immunotherapy expertise; as well as clinical experience in transplantation & cellular therapies. In addition to technical expertise, there is extensive QA/QC and regulatory experience available to ensure FDA compliance during the development of each specific cellular product. CCT staff can provide assistance in the development of standard operating procedures, the performance of process and/or equipment validation, staff training & competency/proficiency assessments, as well as the preparation of regulatory documents including IND applications.