Human Cord Blood Stem Cell-Modulated Regulatory T Lymphocytes Reverse the Autoimmune-Caused Type 1 Diabetes Yong Zhao
Current stem cell-based therapy, along with islet transplantation and promotion of beta-cell regeneration by drugs or trans-differentiation of exocrine cells into islet beta cells, are promising approaches to treat autoimmune-caused type 1 diabetes (T1D). However, autoreactive effector T cells may destroy these newly-generated insulin-producing cells, thereby minimizing their therapeutic potential. A major challenge for treatment of T1D is to identify therapeutic approaches that fundamentally modulate autoimmune responses. Regulatory T cells (Tregs) play a crucial role in maintaining homeostasis and self-tolerance through their inhibitory impact on autoreactive effector T cells. Increasing evidence demonstrates that intrinsic defects in the function of Tregs are associated with initiation and progression of T1D, both in diabetic patients and animal models. Therefore, Treg-based immunotherapy is unlikely to be beneficial for treatment of autoimmune diseases if using defective Tregs. Recently, we have developed a unique technology to reverse established T1D by using human cord blood-derived stem cells (CB-SC) to modulate autologous CD4CD62L Tregs. This treatment not only eliminated hyperglycemia and restored islet architecture via a marked increase in beta-cell proliferation, but also diminished the autoimmunity through systemic immune alterations and local regulations in pancreatic islets. These autologous mCD4CD62L Tregs can be readily generated by co-culture with allogeneic CB-SC for clinical therapeutic applications without concern for immune rejection. It may have implications for developing novel human therapy to safely manipulate the immune system to reverse or prevent T1D.
Mesenchymal Stem Cells in the Treatment of Diabetic Foots Ulcerations Stephanie Wu, DPM, MS; Laura Shin, BS; Lee Rogers, DPM; Nicholas Bevilacqua, DPM; Daniel Peterson, PhD; David Armstrong, DPM, PhD
Foot problems are one of the most common complications in diabetic patients leading to hospitalization. One of the most common components in the causal pathway to limb amputation in persons with diabetes is a neuropathic foot ulcer. Cells in the chronic wound are subjected to chronic inflammation, reactive oxygen species, proteolytic enzymes and recurrent ischemia-reperfusion cycles. These stresses inhibit fibroblast proliferation resulting in a prematurely senescent phenotype populating the wound. Marrow cells have been shown to play an important role in the healing of cutaneous wounds. Subsequent to dermal wounding marrow-derived mesenchymal stem cells (MSC) are mobilized into the peripheral circulation and engraft near adnexal structures in the skin. These cells eventually differential into skin cells. Animal studies have shown wound healing significantly improved after injection of MSC into the wound. Human studies with two recent small case-series transplanting autologous cultured marrow derived MSC and pure marrow aspirate have shown rapid improvement in granulation and healing in chronic wounds. Researchers at Scholl’s Center for Lower Extremity Ambulatory Research and Neuroscience Stem Cell Regenerative Medicine Laboratory Rosalind Franklin University found success with the topical application of marrow aspirate harvested from the distal tibia in 3 patients with slowly responsive wounds secondary to HIV neuropathy, diabetic neuropathy, and mixed arterio-venous disease.of adequate offloading as well as adding an element of “forced compliance” to the prescribed course of pressure reduction. Patients may also benefit from certain prophylactic interventions, including evaluation for surgical interventions to alter their biomechanics and loading. It has been well established that plantar pressure is directly proportional to plantar tissue thickness. Fat pad atrophy is common amongst persons with diabetes, particularly in the forefoot. Augmenting this high-risk area with a biocompatible, viscoelastically robust substance might have the benefit of mitigating pressure and potentially reducing the risk for ulceration.
