Diabetic Foot: Treatment of Chronic Ulcers and Neuropathy With Transplantation of Placenta Derived Stem Cells (PDSC) - A Dose Escalation Safety and Exploratory Efficacy Study

Diabetes mellitus is a global public health threat, with a projected global cost of US $825 billion by 2030 and $845 billion by 2045 (International Diabetes Federation). Angiopathy (macrovascular and / or microvascular) and neuropathy secondary to disease sets the stage for diabetic foot ulceration (DFU) by initiating cycles of inflammation, ulceration, infection, and hospitalization, often resulting in amputation. DFU in the context of a combined neuro-ischemic disease has a worse outcome. In the United States, 54% of all amputations are related to diabetes, and in 85% of cases, the trigger is a DFU, costing $9 to $13 billion per year.

Peripheral vascular disease (PVD) due to arteriosclerosis is also a known cause of ischemic ulcers and is also an aggravating condition of DFU. PVD, either alone or in combination with diabetes, often culminates in amputations and recurrent ulcers that do not heal. Approximately 50% of patients with DFU have concurrent vascular disease. As surgical revascularization is not always feasible in these patients, there is an urgent need to develop alternative therapies capable of improving the blood supply to the ischemic foot.

Cell-based therapies have gained attention as viable options to provide the elements necessary to help restore damaged vessels while inducing the formation of new ones. Cell products may contain endothelial progenitor cells (EPC) and / or mesenchymal stem / stromal cells (MSC), both critical during vascular repair and formation given the structural involvement of EPC and the documented pro-angiogenic activity of MSC. Based on the capabilities of the documented individual cell types for EPC and MSC, the use of a combinatorial cell approach in the same product constitutes an interesting alternative for treating vascular disease. Multiple small clinical studies have used autologous or allogeneic bone marrow mononuclear cells (MNC), either directly after bone marrow extraction or after tissue culture, to treat critical limb ischemia. In general, the therapy resulted in an improvement in symptoms, such as a decrease in pain, and in some studies the ankle / arm index and / or tissue oxygenation improved.

Adipose-derived vascular stromal fraction (AD-SVF) is a viable option to treat vascular disease, given its enrichment in EPC and higher MSC titers compared to other sources, e.g., bone marrow. Logistical advantages complement this key multi-phenotypic display as SVF cells can be obtained from same-day processing of easily accessible harvested adipose tissue without the need for a Good Manufacturing Practice (GMP) processing facility to manufacture an MSC-based product, thus making SVF a "point of care" therapy.

It is difficult to treat vascular disease and chronic ulcers caused by PVD and / or diabetes in resource-poor countries like Nicaragua. Most patients are unable to maintain a limited weight bearing or non-ambulatory state due to the economic imperative of working. Patients often have to travel long distances on poor road conditions to obtain medical care. Revascularization procedures are not economically possible for the majority of the Nicaraguan population. Additionally, advanced stem cell procedures that require cell processing facilities pose significant logistical and economic challenges.