Systemic hair transplant of wild-type hematopoietic stem and progenitor cells (green) caused their distinction into microglia-like cells (red), which lowered the amount of beta amyloid plaques (magenta) in the brain. Credit: Priyanka Mishra and Alexander Silva, UC San Diego Health Sciences
A study from UC San Diego suggests that transplants of hematopoietic stem cells can protect mice with Alzheimers from memory decline, neuroinflammation, and build-up of β-amyloid.
In the continuous mission to find a remedy for Alzheimers disease, a burgeoning branch of medicine offers restored hope. Stem cell treatments, which have actually been effectively applied to a variety of cancers and blood and body immune system disorders, are now being examined for their capacity versus Alzheimers. A recent study conducted by researchers at the University of California San Diego recommends that stem cell transplants could be an appealing therapeutic against Alzheimers.
In the study, just recently released in Cell Reports, the scientists show that transplanting hematopoietic stem and progenitor cells was reliable in rescuing numerous signs and symptoms of Alzheimers in a mouse design of the illness. Mice that received healthy hematopoietic stem cells revealed preserved memory and cognition, decreased neuroinflammation, and significantly less β-amyloid accumulation compared to other Alzheimers mice.
” Alzheimers is a really intricate illness, so any possible treatment has to be able to target several biological pathways,” stated senior research study author Stephanie Cherqui, Ph.D., teacher at UC San Diego School of Medicine. “Our work reveals that hematopoietic stem and progenitor cell transplantation has the potential to prevent complications from Alzheimers and could be an appealing therapeutic avenue for this disease.”
The study was spearheaded by Priyanka Mishra, PhD, (left) and Alexander Silva (ideal), researchers in the Cherqui laboratory at UC San Diego School of Medicine. Credit: UC San Diego Health Sciences
The success of the therapy originates from its effects on microglia, a type of immune cell in the brain. Microglia have actually been linked in the initiation and progression of Alzheimers illness in different methods. Its understood that continual microglia inflammation can contribute to Alzheimers, as the release of inflammatory cytokines, chemokines, and enhance proteins causes increased β-amyloid production. In healthy conditions, microglia also play a major function in clearing β-amyloid plaques, however this function suffers in Alzheimers. The resulting β-amyloid accumulation likewise puts stress on other brain cells, consisting of endothelial cells that affect blood circulation to the brain.
Postdoctoral scientist and first author Priyanka Mishra, Ph.D., set out to test whether transplanting stem cells could lead to the generation of new, healthy microglia that might reduce the development of Alzheimers disease. The Cherqui lab had already found success using comparable stem cell transplants to deal with mouse models of cystinosis, a lysosomal storage illness, and Friedreichs ataxia, a neurodegenerative disease.
Mishra and her colleagues performed systemic hair transplants of healthy wild-type hematopoietic stem and progenitor cells into Alzheimers mice and found that the transplanted cells did separate into microglia-like cells in the brain.
The researchers then evaluated the animals behavior and found that amnesia and neurocognitive disability were entirely prevented in mice that got the stem cell transplant. These mice showed better item recognition and threat perception, in addition to normal stress and anxiety levels and locomotor activity, compared to non-treated Alzheimers mice.
Stephanie Cherqui, PhD, has actually successfully led the clinical screening and commercialization of other therapies established in her laboratory. Credit: UC San Diego Health Sciences
Looking more detailed at the animals brains, the researchers discovered that mice treated with healthy stem cells revealed a substantial reduction in β-amyloid plaques in their hippocampus and cortex. The transplant also led to reduced microgliosis and neuroinflammation and helped maintain the stability of the blood-brain barrier.
The scientists utilized transcriptomic analyses to determine the expression of various genes in treated and non-treated Alzheimers mice. Those that had received the stem cell treatment had less cortical expression of genes related to infected microglia, and less hippocampal expression of genes related to infected endothelial cells.
Completely, the transplantation of healthy hematopoietic stem and progenitor cells caused enhanced microglia health, which in turn protected against numerous levels of Alzheimers pathology.
Importantly, a 3rd group of mice that got stem cells isolated from Alzheimers mice displayed no indications of enhancement, demonstrating that these cells retained the disease-related details in Alzheimers illness.
Future research studies will even more explore how the healthy transplanted cells produced such considerable improvements, and whether similar transplant methods can be utilized to relieve Alzheimers symptoms in humans.
” Alzheimers disease positions a major emotional and economic problem on our society, yet there is no efficient treatment available,” stated Cherqui. “We are thrilled to see such appealing preclinical arise from hematopoietic stem cell therapy and anticipate developing a brand-new therapeutic method for this devastating illness.”
Recommendation: “Rescue of Alzheimers illness phenotype in a mouse model by hair transplant of wild-type hematopoietic stem and progenitor cells” by Priyanka Mishra, Alexander Silva, Jay Sharma, Jacqueline Nguyen, Donald P. Pizzo, Denise Hinz, Debashis Sahoo and Stephanie Cherqui, 8 August 2023, Cell Reports.DOI: 10.1016/ j.celrep.2023.112956.
Co-authors of the study consist of: Alexander Silva, Jay Sharma, Jacqueline Nguyen, Donald P. Pizzo and Debashis Sahoo, all at UC San Diego, as well as Denise Hinz at the La Jolla Institute for Immunology.
The study was moneyed by the Epstein Family Research Collaboration Fund, the Alzheimers Disease Cooperative Study (ADCS) at UC San Diego, the National Institutes of Health, the California Institute for Regenerative Medicine, the Cystinosis Research Foundation, and Friedreichs Ataxia Research Alliance.
Stem cell treatments, which have been successfully applied to a range of cancers and blood and immune system disorders, are now being investigated for their capacity versus Alzheimers. A recent study performed by researchers at the University of California San Diego suggests that stem cell transplants might be a promising restorative versus Alzheimers.
The success of the therapy stems from its results on microglia, a type of immune cell in the brain. Microglia have been implicated in the initiation and development of Alzheimers disease in different ways. The resulting β-amyloid build-up likewise puts tension on other brain cells, including endothelial cells that affect blood circulation to the brain.