Stem cell therapy to save people with spinal cord injury
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Stem cell therapy to save people with spinal cord injury
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Stem cell therapy to save people with spinal cord injury.
Perhaps in the near future, stem cell therapy will really open up a new era of human treatment of spinal cord injury!
Spinal cord injury usually refers to the external influence of the spinal cord, causing partial or total paralysis of the injured site and below, leaving the patient disabled for life.
Spinal cord injury is a relatively common trauma.
For a long time, the treatment of spinal cord injury has been mainly through surgical decompression of the spinal cord to restore its stability, and drugs, hyperbaric oxygen and other treatments to inhibit or reduce its secondary injury.
To a certain extent, the patient’s symptoms were relieved, but no fundamental changes were made in neurological function.
Therefore, there is an urgent need for an efficient and safe treatment plan to change this situation.
Thus, stem cell therapy came into being. The difficulty in the treatment of spinal cord injury lies in: nerve conduction reconstruction and motor function recovery.
On the one hand, the immune system can promote the regeneration of the nervous system, but on the other hand it produces scars to prevent nerve regeneration and connection.
It is generally considered that the treatment window period is 6 months.
Dawn’s emerging stem cell therapy
Because stem cells have strong self-replication ability and paracrine effects, scientists and doctors have placed great hopes on them in the treatment of “spinal cord injury”.
Regarding the mechanism, more and more evidence indicates that there may be two types:
The transplanted cells promote the natural repair of the original damaged tissue by providing cytokines that repair the damage, or prevent the damage from further aggravating.
Transplanted cells replace damaged cells (such as neurons and oligodendrocytes), promote the formation of bridges in the spinal cord injury cavity, guide nerve regeneration, regulate the immune microenvironment, and repair non-nerve tissues in the spinal cord to promote nerve injury recovery.
At present, the global clinical trial projects of stem cell treatment for spinal cord injury use bone marrow mesenchymal stem cells, adipose stem cells, umbilical cord mesenchymal stem cells, nerve cells, oligodendrocyte precursor cells, autologous Schwann cells, and autologous olfactory ensheathing cells .
According to the statistics registered on ClinicalTrials, the world’s largest clinical research database of the National Institutes of Health (NIH), there are 57 clinical trials of cell therapy for spinal cord injury, most of which are in Phase 1 and some are in Phase 2.
Cell therapy for the treatment of spinal cord injury
In clinical trials, the most common cell sources used to treat spinal cord injury are mainly mesenchymal stem cells, neural stem cells, and oligodendrocyte precursor cells.
Mesenchymal stem cells
Mesenchymal Stem Cells (MSCs) are usually derived from bone marrow, adipose tissue, umbilical cord, placenta and other tissues.
Mesenchymal stem cells are easy to separate and expand, and have a variety of biological functions such as immune regulation, anti-apoptosis, angiogenesis, anti-scarring and nutritional support.
In clinical trials, the most common source of cells used to treat spinal cord injury is mesenchymal stem cells.
According to statistics, the clinical results of mesenchymal stem cells for spinal cord injury show no obvious side effects and have certain therapeutic effects [2-4].
In 2015, Dai Jianwu’s team from the Institute of Genetics of the Chinese Academy of Sciences carried out the world’s first clinical study of nerve regeneration collagen scaffold combined with bone marrow mononuclear cells (including BMSC) transplantation to treat spinal cord injury.
Five cases of spinal cord injury repair operations have been performed in three clinical hospitals, and the safety has been affirmed.
In addition to the role of stem cells, the nerve regeneration collagen scaffold is indispensable, avoiding cell proliferation and improving the therapeutic effect of stem cells.
In 2017, Rong Limin’s team from the Third Affiliated Hospital of Sun Yat-sen University launched mesenchymal stem cells to treat spinal cord injury.
Currently, Rong Limin’s team is in charge of the project “Clinical trials and mechanism research of intrathecal injection of human allogeneic umbilical cord mesenchymal stem cells for spinal cord injury”.
They released a clinical research plan for stem cell treatment of early chronic spinal cord injury [5-6] and carried out more than 100 clinical trials.
In 2019, Japan conditionally approved the listing of a mesenchymal stem cell therapy for spinal cord injury-Stemirac.
First, about 50 ml of bone marrow blood is drawn from the patient, and mesenchymal stem cells are obtained, and then expanded to 50 to 200 million in vitro, and intravenously injected into the patient within 3-8 weeks after the injury, in order to achieve treatment effect.
Neural stem cells
Neural Stem Cells (NSC) are stem cells in the nervous system that can self-renew and evolve into differentiated precursor cells to generate neurons and glial cells, such as astrocytes and oligodendrocytes .
In 1992, Reynolds and Weiss first isolated neural stem cells from mouse striatum. The discovery of neural stem cells brings new hope for the treatment of spinal cord injury.
The transplanted neural stem cells can fill the residual cavity after spinal cord injury and differentiate into neurons, astrocytes and oligodendrocytes in the body to provide remedy Sheathing and new nerve connections maintain the integrity of nerve fibers.
Stem Cells Inc. is the first company in the world to develop neural stem cells (from the brain tissue of aborted fetuses) to treat spinal cord injury.
Some patients have improved sensory functions. However, Stem Cells Inc. terminated the Phase 2 clinical trial of stem cells for spinal cord injury in May 2016 due to some reasons.
Neural stem cells can also be obtained by differentiation of induced pluripotent stem cells (iPSCs).
Currently, Keio University in Japan is carrying out iPSC-derived neural stem cells to treat spinal cord injury, and observe its safety and effectiveness for a period of one year.
Compared with naturally obtained neural stem cells, neural stem cells derived from iPSCs have the advantages of mass production and autologous transplantation [7].
Oligodendrocyte precursor cells
Oligodendrocyte (OL) is the myelinating glial cell of the central nervous system, while OPC is the starting cell for the development of the oligodendrocyte lineage.
It is an immature OL with strong proliferation ability . OPC can proliferate, migrate, and differentiate into mature oligodendrocytes in the body, and form myelin sheath to function.
OPC is suitable for the treatment of spinal cord injury. It responds quickly to injury and can self-renew. It is an important part of injury repair.
Animal experiments have shown that transplanted OPC can promote white matter retention, increase the number of endogenous oligodendrocytes, reduce the volume of the cavity, and thereby improve exercise recovery.
The underlying therapeutic mechanism of OPC may be remyelination, regulation of the local immune microenvironment, secretion of neurotrophic factors, and provision of physical scaffolds to support growing axons.
OPC can secrete a series of substances, including growth factors, neurotrophic factors, chemokines and cytokines.
Whether OPC treats spinal cord injury is due to the secretory function or the remyelination function, it is still unclear. Because it is difficult to obtain the original OPC, its source is still one of the problems to be solved in its clinical application.
Pluripotent stem cells (PSC), including embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC), can obtain a large amount of OPC through targeted differentiation.
Pluripotent stem cells can expand indefinitely in vitro, have strong differentiation potential, and theoretically can form any kind of cell in the body.
In 2009, the US FDA approved a clinical trial to treat spinal cord injury using OPC cells derived from embryonic stem cell differentiation. Later, the project was terminated due to financial reasons.
Asterias Biotherapeutics continues to conduct a clinical trial of stem cell therapy for spinal cord injury.
The core part of this therapy is AST-OPC1, an OPC derived from human embryonic stem cells. 1/2a clinical trials show that AST-OPC1 has good safety and can improve the patient’s exercise capacity.
However, OPC1, as the source of embryonic stem cells, requires consideration of immune rejection.
In 2020, the domestic stem cell company Sanqi Biotechnology and its wholly-owned subsidiary Sanqi Pharmaceutical developed a transdifferentiation method (PCT/CN2014/087828), which can use small molecule compounds to convert human fibroblasts into OPCs.
Its advantage lies in its own non-rejection, high conversion efficiency, and certain cost advantages.
Unfortunately, large-scale production is not yet possible. This method is expected to develop an innovative treatment for spinal cord injury based on autologous OPC.
Summary
The exploration of stem cell therapy for spinal cord injury has never stopped. How to make stem cell therapy more safe and effective for spinal cord injury is what scientists and cell therapy developers are doing.
For all patients with spinal cord injury, every meaningful clinical trial progress, whether it is a small step or a big step, will change the pace of their lives.
Stem cell therapy to save people with spinal cord injury
(source:chinanet, reference only)
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