A examine from UC San Diego signifies that transplants of hematopoietic stem cells can defend mice with Alzheimer’s from reminiscence decline, neuroinflammation, and accumulation of β-amyloid.
In the continual quest to discover a treatment for Alzheimer’s illness, a burgeoning department of medication provides renewed hope. Stem cell remedies, which have been efficiently utilized to a variety of cancers and blood and immune system problems, at the moment are being investigated for his or her potential towards Alzheimer’s. A current examine performed by scientists on the University of California San Diego means that stem cell transplants might be a promising therapeutic towards Alzheimer’s.
In the examine, not too long ago printed in Cell Reports, the researchers reveal that transplanting hematopoietic stem and progenitor cells was efficient in rescuing a number of indicators and signs of Alzheimer’s in a mouse mannequin of the illness. Mice that obtained healthy hematopoietic stem cells confirmed preserved reminiscence and cognition, decreased neuroinflammation, and considerably much less β-amyloid build-up in comparison with different Alzheimer’s mice.
“Alzheimer’s is a very complex disease, so any potential treatment has to be able to target multiple biological pathways,” mentioned senior examine creator Stephanie Cherqui, Ph.D., professor at UC San Diego School of Medicine. “Our work shows that hematopoietic stem and progenitor cell transplantation has the potential to prevent complications from Alzheimer’s and could be a promising therapeutic avenue for this disease.”
The success of the remedy stems from its results on microglia, a kind of immune cell within the mind. Microglia have been implicated within the initiation and development of Alzheimer’s illness in numerous methods. It’s identified that sustained microglia irritation can contribute to Alzheimer’s, as the discharge of inflammatory cytokines, chemokines, and complement proteins results in elevated β-amyloid manufacturing. In healthy circumstances, microglia additionally play a significant position in clearing β-amyloid plaques, however this operate is impaired in Alzheimer’s. The ensuing β-amyloid build-up additionally places stress on different mind cells, together with endothelial cells that have an effect on blood stream to the mind.
Postdoctoral researcher and first creator Priyanka Mishra, Ph.D., got down to take a look at whether or not transplanting stem cells might result in the era of latest, healthy microglia which may scale back the development of Alzheimer’s illness. The Cherqui lab had already discovered success utilizing related stem cell transplants to deal with mouse fashions of cystinosis, a lysosomal storage illness, and Friedreich’s ataxia, a neurodegenerative illness.
Mishra and her colleagues carried out systemic transplantations of healthy wild-type hematopoietic stem and progenitor cells into Alzheimer’s mice and located that the transplanted cells did differentiate into microglia-like cells within the mind.
The researchers then evaluated the animals’ habits and located that reminiscence loss and neurocognitive impairment have been utterly prevented in mice that obtained the stem cell transplant. These mice confirmed higher object recognition and threat notion, in addition to regular anxiousness ranges and locomotor exercise, in comparison with non-treated Alzheimer’s mice.
Looking nearer on the animals’ brains, the researchers discovered that mice handled with healthy stem cells confirmed a major discount in β-amyloid plaques of their hippocampus and cortex. The transplant additionally led to decreased microgliosis and neuroinflammation and helped protect the integrity of the blood-brain barrier.
Finally, the researchers used transcriptomic analyses to measure the expression of various genes in handled and non-treated Alzheimer’s mice. Those that had obtained the stem cell remedy had much less cortical expression of genes related to diseased microglia, and fewer hippocampal expression of genes related to diseased endothelial cells.
Altogether, the transplantation of healthy hematopoietic stem and progenitor cells led to enhanced microglia health, which in flip protected towards a number of ranges of Alzheimer’s pathology.
Importantly, a 3rd group of mice that obtained stem cells remoted from Alzheimer’s mice exhibited no indicators of enchancment, demonstrating that these cells retained the disease-related info in Alzheimer’s illness.
Future research will additional discover how the healthy transplanted cells produced such vital enhancements, and whether or not related transplant methods can be utilized to alleviate Alzheimer’s signs in people.
“Alzheimer’s disease poses a major emotional and economic burden on our society, yet there is no effective treatment available,” mentioned Cherqui. “We are excited to see such promising preclinical results from hematopoietic stem cell therapy and look forward to developing a new therapeutic approach for this devastating disease.”
Reference: “Rescue of Alzheimer’s disease phenotype in a mouse model by transplantation 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.
Co-authors of the examine embrace: Alexander Silva, Jay Sharma, Jacqueline Nguyen, Donald P. Pizzo and Debashis Sahoo, all at UC San Diego, in addition to Denise Hinz on the La Jolla Institute for Immunology.
The examine was funded by the Epstein Family Research Collaboration Fund, the Alzheimer’s Disease Cooperative Study (ADCS) at UC San Diego, the National Institutes of Health, the California Institute for Regenerative Medicine, the Cystinosis Research Foundation, and Friedreich’s Ataxia Research Alliance.