Stem cell therapy for stroke and other neurodegenerative diseases
By linking together basic and clinical research, we aim to clarify cellular mechanisms of regeneration following damage to the brain and develop new therapeutic strategies to restore function in this organ (primarily in stroke and Parkinson’s disease) by transplantation of stem cells or reprogrammed cells and optimization of endogenous repair mechanisms.
Available experience, intellectual potential and manpower, technology platforms, transgenic animals, methodological and clinical “know-how”, and close interaction between clinicians and basic scientists provide added value, strongly supporting the feasibility of our work. We are transplanting different types of neuroblasts generated either from human skin cell-derived induced pluripotent stem (iPS) cells or via direct conversion of skin cells to neurons (iN cells) (Fig.1).
Reprogramming of somatic (e.g., skin) cells is an emerging technology which gives the possibility to develop any cell type avoiding the ethical concerns with the use of human embryonic stem (ES) cells. In addition, using iPS and iN cell technology patient-specific cells can be generated for transplantation, avoiding the need for immunosuppression and risk for rejection. We are already capable to generate neurons by iPS and iN cell technology. In addition, we work with endogenous neural stem cells, which participate in post-stroke recovery and can replace lost neurons. Exploration of mechanisms regulating this self-repair process, which was discovered by us (Arvidsson et al., 2002, Nature Medicine; 1009 citations), and definition of ways to modulate this response by which it could be developed into an efficient therapeutic tool is a major goal of our research. We also determine how inflammation associated with ischemic brain damage influences the generation and integration of neurons derived from stem cells and reprogrammed cells, and how the beneficial effects of innate and adaptive immune system should be promoted to improve functional recovery.
Finally, we continue our work with the clinical translation of stem cells in patients with Parkinson’s disease. The outcome of this work has a major impact on neuronal replacement strategies also in other brain disorders such as stroke.
Our laboratory for the first time combines transplantation of stem cells, stimulation of endogenous neurogenesis and modulation of inflammatory responses in order to develop clinically effective cell replacement therapies for human neurodegenerative diseases. Such diseases represent leading causes of disability, and with the growing aging population, their economical and societal burden will be further increased.
If our objectives are achieved, this work will have major therapeutic implications for patients with neurodegenerative disorders such as stroke and Parkinson’s disease.