Mesenchymal Stem Cells in the Brain
Mesenchymal Stem Cells: A CNS Therapy Candidate
Mesenchymal stem cells (MSCs) are multipotent cells that can be isolated from several adult tissues, including bone marrow, umbilical cord blood, and adipose tissue. They have a number of advantageous traits that make them a strong candidate for the new generation of cell-replacement therapy (CRT) — even for central nervous system (CNS) disorders.
CRT for CNS disorders faces several major obstacles: successfully delivering therapeutic/stem cells to damaged areas or lesions within the CNS, avoiding the host’s immune response against allogenic cells, and preventing ectopic tissue formation. MSCs have unique characteristics that can overcome these obstacles. They can differentiate into multiple tissue-specific lineage cells, act as progenitor-cell bioreactors that produce soluble factors to promote tissue regeneration, and modulate the immune system. MSCs are also considered immunoprivileged — they have low expression of class II Major Histocompatibility Complex (MHC-II) and other immune-stimulatory molecules on their cell surface. This article focuses on how MSCs are being used to treat two CNS diseases in particular: multiple sclerosis (MS) and ischemic stroke (IS).
Bone marrow derived (BM-MSCs) and adipose derived mesenchymal stem cells (AD-MSCs) have both shown promising results — BM-MSCs in an experimental autoimmune encephalomyelitis (EAE) preclinical model of MS, and AD-MSCs in the permanent middle cerebral artery occlusion (pMCAO) model of IS.
MSCs in Ischemic Stroke
IS occurs when an obstruction blocks a blood vessel supplying a region of the brain, damaging neurons and astroglia in that region. Replacing these cells and repairing the damaged tissue has become a major research goal, turning IS clinical research toward stem cell therapy.
A recent study by Gutierrez-Fernandez’s group found that AD-MSCs are just as restorative as BM-MSCs at promoting recovery, repair, and brain protection in IS rat models. Intravenous administration of allogenic AD-MSCs and BM-MSCs produced significant functional recovery, decreased apoptosis, and increased expression of neurogenesis, synaptogenesis, angiogenesis, and oligodendrogenesis markers. These results suggest a less invasive route for administering therapeutic cells. But further studies on the fate of the administered cells are needed before this method can be considered for clinical use.
MSCs in Multiple Sclerosis
MS is a chronic, immune-mediated demyelinating disease of the CNS, marked by demyelinated plaques in the brain and spinal cord. MS plaque formation involves immune-cell infiltration, damage to oligodendrocytes and their failure to remyelinate, axon degeneration, and eventually astrocytosis. There is still no cure for MS. Current disease-modifying therapies only partially reduce the frequency and severity of relapses, and rely on immunomodulation. As a result, MS researchers have turned their attention to therapies that not only stop the autoimmune attack, but also replace destroyed CNS cells with properly functioning ones through CRT.
Using Patients’ Own Cells: MSC-Derived Neural Progenitors
Several recent studies report promising results for autologous, culture-expanded MSC transplantation in MS models. Based on Harris’s publication in Stem Cells Translational Medicine, intrathecal delivery of Bone marrow mesenchymal stem cell-derived neural progenitors (MSC-NPs) is a promising strategy for cell-based therapy in MS. MSC-NPs derived from both MS patients and healthy controls showed the same properties that support MSCs’ therapeutic potential in the CNS, regardless of donor disease status.
Like MSCs, MSC-NPs secrete immunomodulatory factors — including cytokines and growth factors such as TGF-β, IL-6, IL-10, HGF, heme oxygenase-1, and nitric oxide — that inhibit T-cell proliferation and promote naïve CD4+ T-cell polarization into FoxP3+ T cells. MSC-NPs also share MSCs’ trophic effects, secreting factors like HGF, IGF-1, SDF1α, and VEGF that promote oligodendroglial differentiation of neural stem cells. They’re also neuroectodermally committed with reduced capacity for mesodermal differentiation, lowering the risk of abnormal tissue formation — making them a more suitable candidate for cell-based CNS injury therapy.
One of the most significant aspects of this study is the possibility of using an MS patient’s own cells as the therapeutic source. This reduces immune response, and the adult stem cells present in these patients also show genetic stability. Together, these findings point to several promising genetic and cellular therapeutic strategies worth investigating in the near future.
Further Reading
- Characterization of autologous mesenchymal stem cell-derived neural progenitors as a feasible source of stemcells for central nervous system applications in multiple sclerosis.
- Effects of intravenous administration of allogenic bone marrow- and adipose tissue-derived mesenchymal stem cells on functional recovery and brain repair markers in experimental ischemic stroke
- Mesenchymal stem cell transplantation in multiple sclerosis.
- Immunosuppressive properties of mesenchymal stem cells: advances and applications.
