Neural stem cells in development & neurological disorders
Transplantation of various types of stem cells have anti-inflammatory effects that control inflammation and promote recovery. Our lab studies human bone marrow mesenchymal stem cell (MSC) because they are anti-inflammatory and resist rejection even as allogenic transplants. MSC mitigate immune rejection of non-autologous transplants, which can be fatal, for example in Graft vs. Host Disease (GvHD), which often occurs after transplantation of hematopoietic stem cells to reconstitute blood cell production. Uncontrolled inflammation plays a major role in many disorders and injuries, such as spinal cord injury (SCI), and MSC restore a more normal balance between pro- and anti-inflammatory factors.
A major challenge in MSC therapy delivered systemically, for example intravenously, is that the cells get trapped rapidly in major organs including the lungs, liver, spleen etc. The MSC survive transiently and their fate is uncertain. We encapsulate MSC in alginate capsules, which allows anti-inflammatory and growth factors secreted by the cells to enter the host while the capsules protect the MSC from attack by the host. We transplanted MSC in capsules by minimally invasive lumbar delivery into SCI rats and the observed anti-inflammatory effects in the injury site and improved functional recovery. The MSC were maintained in capsules more than 2 cm from the SCI site indicating that the effects are due to secreted factors “acting at a distance” from their site of transplantation. Encapsulated MSC survived in vivo for 2 months and are active after retrieval from animals. Ongoing experiments are exploring encapsulated MSC in other inflammatory disorders. In addition, we are developing systems to scale-up production of encapsulated MSC for pre-clinical studies to treat large mammals.