Stem Cell Therapy for Alzheimer’s Disease
Alzheimer’s disease (AD) is characterized by progressive loss of cognitive functioning. There are currently 36 million people afflicted by this condition worldwide, and that number is expected to triple by the year 2050. Treatment of AD poses many challenges, as it is degenerative and not curable. Stem cell therapy has shown some promise in treating AD, and many recent studies support the use of stem cells as a viable option for Alzheimer’s disease.
Stem cells have been used successfully to counteract the symptoms of AD. Multipotent stem cells can differentiate into many cell types, such as oligodendrocytes, astrocytes, and neurons. These cells are derived from umbilical cord tissue and blood, amniotic fluid, bone marrow, and adipose (fat) tissue. With cell technology, stem cells can generate differentiate into types of glial and neuronal cells that are needed in AD treatment.
How Stem Cells Work
In mouse subjects with AD, studies show that transplanted stem cells change into mature cell types that improve memory and learning. One clinical study showed improvements of cholinergic neuron numbers, as well as memory in such AD rats after being transplanted with stem cells. It is thought that differentiation, maturation, and integration of the stem cells lead to secreted factors that signal molecules to stimulate cholinergic neurogenesis, and possible, prevent further loss. It has been shown that stem cell grafts increase brain-derived neurotrophic factor levels, and also, lead to behavioral rescue in mouse models of AD.
Grafted stem cells also are thought to work by altering the microenvironment in animal subjects’ brains. This process may have a negative impact on the therapeutic effect of stem cell transplantation. Nerve growth factors could promote survival of the cells, and stem cells transduced with human nerve growth factor genes can integrate into the cerebral cortex of AD rats to enhance cognitive performance. Transplantation of stem cells is used to deliver potent therapeutic agents, as well. These include insulin-degrading enzyme, neprilysin, plasmin, and cathepsin B.
Neural stem cells express high levels of neurotrophins, such as NGF and BDNF. Stem cells deliver neurotropins to the diseased brain, possibly modulating endogenous synaptic plasticity and enhancing survival of neurons. Many clinical studies support this notion, and stem cell transplantation has also been seen to increase hippocampal synaptic density and improve learning and memory in many transgenic models. The enhancement of synaptic growth was found to reduce neuronal loss and elevate levels of glial-derived neurotrophic factor within the brain.
Chronic inflammation is thought to play an important role in AD. Certain stem cell populations can exhibit robust anti-inflammatory properties. Stem cells have been found to induce expression of certain anti-inflammatory factors, such as prostaglandin E2 and interleukin-10. Peripheral administration of human umbilical cord blood stem cells was shown to reduce AD pathology by a mechanism that involves modulation of CD40 signaling. There is growing evidence that stem cells will also modulate the immune system. Because AD is an inflammation-associate condition, stem cells may reduce migrogliosis and expression of proinflammatory cytokine tumor necrosis factor. A few clinical studies suggest that mesenchymal stem cells can positively influence inflammation in AD models.
In a research study, embryonic stem cells were evaluated, a murine brain injury received a transplantation. The cells were capable of maturing into cholinergic and GABAergic neuronal subtypes and synaptically integrated with host neuronal circuits. This lead to improvements in impaired spatial memory and learning. Stem cells were also found to work in a rodent model study to decrease neuroinflammation, reverse cognitive deficits, and attenuate certain neuropathology. Intravenously, stem cells are capable of crossing the blood-brain barrier, and they can migrate to regions of neural injury. This has been done successfully in several studies.
Researchers recently used umbilical cord blood stem cells in an open-label phase I clinical trial. Nine patients with AD were given treatment. At three months, no patient had any serious adverse event from surgical transplantation of stem cells. Umbilical cord stem cells were also used to express high levels of angiogenic growth factors, which shown migratory activity. Overall, stem cell therapy for AD has enormous promise but more research is needed. MSC-based therapies have been best for human clinical trials.
Bone marrow stem cells have been found in one study to increase in number of positive cells for choline acetyltransferase. In addition, these cells removed AB plaques from the hippocampus and reduced substance deposits in AD mouse models. Human stem cells were found to enhance autophagy, promote AB clearance, and increase neuronal survival in another study. Intravenously injected stem cells were found in the brain for up to 12 days following the injection in animal models, and one report suggested that adipose-derived MSCs improve ACH levels, cognitive function, and locomotor ability in aged mice. The beneficial effects of stem cells were also associated with activation of M2-like microglia.
R3 Stem Cell offers regenerative therapy for Alzheimer’s disease at several of its 34 Centers nationwide. Call (844) GET-STEM today for a complimentary consultation to see if you are a candidate!
Chen WW & Blurton-Jones M (2012). Concise Review: Can Stem Cells be used to Treat or Model Alzheimer Disease? Stem Cells, 30(12), 2612-2618.
Chen J., Tang Y.X., Liu Y.M., Hu X.Q., Liu N., Wang S.X., Zhang Y., Zeng W.G., Ni H.J., Zhao B., et al. Transplantation of adipose-derived stem cells is associated with neural differentiation and functional improvement in a rat model of intracerebral hemorrhage. CNS Neurosci. Ther. 2012;18:847–854. doi: 10.1111/j.1755-5949.2012.00382.x.
Darlington D., Deng J., Giunta B., Hou H., Sanberg C.D., Kuzmin-Nichols N., Zhou H.D., Mori T., Ehrhart J., Sanberg P.R., Tan J. Multiple low-dose infusions of human umbilical cord blood cells improve cognitive impairments and reduce amyloid-β-associated neuropathology in Alzheimer mice. Stem Cells Dev. 2013;22:412–421. doi: 10.1089/scd.2012.0345.
Duncan T & Valenzuela M (2017). Alzheimer’s disease, dementia, and stem cell therapy. Stem Cell Res Ther, 8, 111.
Ha S., Ahn S., Kim S., Joo Y., Chong Y.H., Suh Y.H., Chang K.A. In vivo imaging of human adipose-derived stem cells in Alzheimer’s disease animal model. J. Biomed. Opt 2014;19:051206.
Honmou O., Houkin K., Matsunaga T., Niitsu Y., Ishiai S., Onodera R., Waxman S.G., Kocsis J.D. Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke. Brain. 2011;134:1790–1807.
Lee J.K., Jin H.K., Bae J.S. Bone marrow-derived mesenchymal stem cells reduce brain amyloid-β deposition and accelerate the activation of microglia in an acutely induced Alzheimer’s disease mouse model. Neurosci. Lett. 2009;450:136–141. doi: 10.1016/j.neulet.2008.11.059.
Salem A.M., Ahmed H.H., Atta H.M., Ghazy M.A., Aglan H.A. Potential of bone marrow mesenchymal stem cells in management of Alzheimer’s disease in female rats. Cell Biol. Int. 2014 doi: 10.1002/cbin.10331.
Shin J.Y., Park H.J., Kim H.N., Oh S.H., Bae J.S., Ha H.J., Lee P.H. Mesenchymal stem cells enhance autophagy and increase β-amyloid clearance in Alzheimer disease models. Autophagy. 2014;10:32–44.
Tong LM, Fong H, & Huang Y (2015). Stem cell therapy for Alzheimer’s disease and related disorders: current status and future perspectives. Experimental & Molecular Med, 47, 151.
Yang H., Xie Z., Wei L., Yang S., Zhu Z., Wang P., Zhao C., Bi J. Human umbilical cord mesenchymal stem cell-derived neuron-like cells rescue memory deficits and reduce amyloid-β deposition in an AβPP/PS1 transgenic mouse model. Stem Cell Res. Ther. 2013;4:76. doi: 10.1186/scrt227