Research progress of stem cell therapy in Alzheimer's disease

Alzheimer's disease is a degenerative disease
of the central nervous system.
It is clinically characterized by progressive cognitive decline and behavioral impairment with characteristic neuropathological changes, often with neuroinflammatory plaques and nerve fiber tangles
.

The current treatment mostly adopts symptomatic comprehensive treatment methods, aiming to reduce the symptoms of decline and delay the development of the disease, but it cannot really play a curative or preventive role
.

Stem cells are a type of cells with self-renewal and multi-directional differentiation potential, which can be divided into totipotent stem cells, pluripotent stem cells, unipotent stem cells, etc
.
according to the differentiation potential.

Stem cell therapy uses stem cells derived from autologous or allogeneic sources to form cells, exosomes, tissues or organs in vitro through isolation, culture, directional induction, etc.
, and then implants them into the human body for treatment
.

Due to the strong differentiation ability of stem cells to different types of nerve cells, glial cells, etc.
, stem cell therapy has become a new idea
for the treatment of Alzheimer's disease.

Possible mechanisms of stem cell therapy include the promotion of endogenous cell regeneration and tissue repair, exogenous stem cell replacement therapy, and regulation of inflammatory
responses.

After stem cells are transplanted into the body, they can not only differentiate and replace damaged nerve cells, but also secrete a series of neurotrophic factors through autocrine or paracrine action, improve the neural microenvironment, and promote the regeneration of nerve cells and synapses; Inhibits neuroinflammation
by modulating glial cells.

In the treatment of Alzheimer's disease, stem cells commonly used include mesenchymal stem cells, neural stem cells and induced pluripotent stem cells
.

Embryonic stem cells are isolated from the inner cell mass of the blastocyst, and the differentiation is totipotent, capable of differentiating into almost all types of cells
.
Transplantation has yielded few experimental results in animal models of Alzheimer's disease, and most preclinical studies have been conducted
using embryonic stem cells as a source of transplanted cells.

The commonly used ways to obtain mesenchymal stem cells include human adipose tissue, umbilical cord blood, bone marrow, amniotic fluid, etc.
, and its characteristics such as wide source and easy acquisition have attracted more attention
from researchers.
It can β amyloid and regulate inflammatory response, induce nerve regeneration, anti-apoptosis, anti-tau, promote DNA repair, etc
.

Neural stem cells are pluripotent stem cells that can differentiate into neurons, glial cells, etc
.
Animal experiments have shown that transplanted neural stem cells can improve brain metabolism and cerebral blood flow
by regulating the activity of microglia, secreting neurotrophic factors, and reducing amyloid in the brain of mice.

Induced pluripotent stem cells can express the specific surface antigens of human embryonic stem cells, while exhibiting high telomerase activity and multiple differentiation potential, and can differentiate into all cell types
of 3 germ layers.

At present, there are nearly 20 clinical trials of stem cell therapy for Alzheimer's disease registered in clinicaltrials.
gov worldwide, mainly mesenchymal stem cell research, mostly in phase I/II.
stage, and most of them are still in progress
.

Summary and outlook

Stem cell therapy has been proven to play a role in many mechanisms in the preclinical model of Alzheimer's disease, but the effective data support of clinical research is still insufficient, and its clinical application is also limited by many factors.

The first is ethics
.
For example, embryonic stem cells are mostly isolated from the blastocyst stage of the embryo, so the source of cells in clinical applications is very limited and controversial
.
Second, tumorigenicity needs to be clear
.
The unlimited proliferative ability of embryonic stem cells makes it prone to the formation of teratomas during transplantation; Induced pluripotent stem cell transplantation has also been found to be at risk of teratoma and cancer formation, and the results of a large animal model suggest that undifferentiated induced pluripotent stem cells may form teratomas, while induced pluripotent stem cell-derived progenitor cells can produce functional tissues
in vivo.
Third, the optimal timing for stem cell therapy needs to be clarified
.
Fourth, the mechanism of action such as survival rate, mobility and differentiation ability of stem cell transplantation in vivo still needs more data support and elucidation
.
Fifth, immune rejection
.
Induced pluripotent stem cells may cause gene dysregulation after gene recombination, so transcription and epigenetics are unstable and may trigger immune rejection.
Stem cells of allogeneic origin can also cause immune rejection
.

Therefore, before conducting clinical trials, it is necessary to conduct actual examination of these problems and conduct more in-depth research on the mechanism, safety and efficacy of stem cells in order to truly exclude the risks of cell transplantation treatment and apply them
to the clinic.