Stem cells have multidirectional differentiation potential, low immunogenic cells, and have a strong immune regulatory function, participating in natural and acquired immune processes. Stem cell therapy has become another high-tech treatment after drug intervention and surgical intervention, and has carried out clinical trials and applications worldwide. Today let’s take a look at the progress of stem cell therapy in various aspects.
- Hematopoietic stem cells-bone marrow transplantation
Hematopoietic stem cell transplantation, also known as bone marrow transplantation, is the earliest and relatively mature stem cell therapy. It is mainly used to supplement damaged hematopoietic stem cells in vivo after radiotherapy or chemotherapy, and then remodel the whole hematopoietic system. Initially and most commonly, allogeneic hematopoietic stem cell transplantation remains a major clinical challenge because of the difficulty in matching and immune rejection. Gene therapy based on hematopoietic stem cells can solve this problem well. In this case, we can purify CD34+ positive hematopoietic stem cells from patients’ bone marrow and peripheral blood by molecular marker CD34, and then insert into their genome to construct a viral vector carrying the target gene, so as to obtain healthy hematopoietic stem cells for transfusion into patients. Over the past two decades, hematopoietic stem cell-based gene therapy has become a more effective treatment for monogenic genetic diseases, such as primary immunodeficiency, hematopathy, and neurometabolic disorders. However, gene therapy based on hematopoietic stem cells also has its drawbacks. Firstly, the whole treatment process is complicated, involving the collection, transport, editing and preservation of cells, which requires the establishment of perfect quality control standards. Secondly, patients need to undergo chemotherapy to remove the original hematopoietic stem cells before receiving transplantation. Therefore, the dose control of chemotherapy also needs to formulate corresponding standards. More lethally, enhancers of viral vectors may inadvertently activate endogenous proto-oncogenes in the process of gene modification using gamma-retrovirus, which can lead to malignancy.
- Treatment of Amyotrophic Lateral Sclerosis (ALS) with pluripotent stem cells
With the technological innovation of stem cells, there is hope for patients with neurological diseases, which support neurons and peripheral cells by releasing neurotrophic factors or direct cell replacement. ALS is a typical representative of motor neuron disease. Because the mechanism of motor neuron degeneration is not yet clear, there is no effective intervention for this disease. At present, stem cell therapy has become an effective method to intervene in ALS, which has attracted widespread social attention. Traditional medicines can not relieve symptoms or reverse the trend of progressive deterioration, and are prone to side effects in some patients. In recent years, stem cell research has opened a new avenue for nerve repair and regeneration, and is one of the effective methods to intervene in degenerative diseases of the central nervous system such as ALS. In neurodegenerative diseases, the main goals of stem cell therapy are cell replacement and neuroprotection. Pluripotent stem cells directly replace motor neurons and diseased glia or provide support to slow their degeneration.
Five mechanisms of stem cell therapy intervention in ALS:
(1) Cell replacement: replace degenerated motor neurons with new functional motor neurons, protect and support motor neurons, and restore neurological function.
(2) Delivery of trophic factors: secrete normal neurons and a variety of cytokines, improve the nigrostriatal system, and promote tissue repair in damaged areas.
(3) Immune regulation: by reducing the production of antibodies by B cells, reducing or inhibiting the activation of DCs and T cells, inhibiting NK secretion of cytokines to regulate immune cell function and reduce the inflammatory response.
(4) Homing: provide cell sources that survive and home to the injured area, differentiate into expected cell types, improve the microenvironment in the brain, and reconstruct the neurological functional areas and conduction pathways.
(5) Exosome secretion: stem cells have high secretion capacity of exosomes, exosomes have anti-neuroinflammation ability, and functional repair and neurovascular reconstruction ability.
3. Epidermal stem cells in the treatment of burns
Epidermal stem cells are a group of adult stem cells located in the basal layer of the epidermis, which can differentiate into various cell types in the epidermis. At present, human epidermal keratinocyte transplantation has become a routine means of tertiary burn treatment. Early studies have found that human epidermal keratinocytes contain three cell types, holoclone, meroclone and paraclone, with decreasing cloning ability and cell stemness. Now we know that holoclone is the key to the success of the epidermal stem cell transplantation experiment, and neither of the other two types of cells can achieve long-term epidermal renewal. Likewise, corneal limbal cells also contain a type of corneal epithelial stem cell, which is essential for the repair of corneal damage. Corneal limbus loses its stem cells in the case of chemical burns, and angiogenesis, chronic inflammation, corneal opacity, and bulbar conjunctival invasion occur in the cornea of the eye, which in turn causes vision loss. Limbal cell transplantation can effectively promote corneal regeneration and visual recovery. Usually, 1-2 square millimeters of limbus extracted from the patient’s uninjured eye can be cultured in vitro to regenerate a complete corneal epithelium for autotransplantation into the injured eye.
4. Mesenchymal stem cell (MSC) therapy
Researchers have discovered a class of cells with cloning ability in bone marrow that can differentiate into cartilage, bone, hematopoietic support matrix and bone marrow adipocytes. Given their pluripotency and ability to differentiate into mesodermal connective tissues outside their lineage, such as muscle, tendon, ligament and adipose tissue, these cells have been named mesenchymal stem cells. Although the theoretical basis of MSCs is not solid, they have been used in more than 900 clinical trials to treat various types of diseases. They disappear soon after transplantation, probably by paracrine means. From a few published experimental results, the therapeutic effect of MSCs is often less than expected. However, there are a few successful clinical cases of MSC therapy. For example, bone marrow stem cell transplantation is used to treat massive bone loss and pulp regeneration.
Behind the success stories of stem cell therapy are decades of in-depth basic research that paves the way, including the biological characteristics of stem cells themselves, their differentiation lineages and signaling mechanisms. Meanwhile, these successes also require practical clinical treatment options. Hematopoietic stem cell transplantation only requires relatively simple intravenous injection, while epidermal stem cells need to be transplanted to the appropriate location of the skin, while the central nervous system-related stem cell therapy operation is more complex.