Sign in to follow this  
Followers 0
  • entries
    180
  • comments
    0
  • views
    113,995

Clinical application of stem cell therapy (Part Two)

Sign in to follow this  
Followers 0
qxcvbnmy

20 views

1.3. Blood system diseases

HSC was first used for blood diseases, and it is the most mature. Both autogenous HSC and foreign HSC are used. And they are mainly used for some hematological malignancies, such as acute myeloid leukemia, acute lymphocytic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, aplastic anemia, etc. All have achieved good results and improved the 10-year survival rate of patients, but it is ineffective for some patients, such as low diploid leukemia. Hematopoietic stem cell transplantation is generally used after chemotherapy. It can differentiate into myeloid progenitor cells, lymphoid progenitor cells, etc. in the human body, and then produce blood cells of various lineages. The treatment of blood system diseases is mainly through cell replacement. Eventually The effect is to rebuild the functional hematopoietic system and immune system. It is now found that multiple myeloma and sickle cell disease can also benefit from HSCs transplantation. For patients with poor conventional treatment or relapse, stem cell transplantation is still effective and can improve the cure rate. However, before transplantation, the patient's physical tolerance, blood system status and human leukocyte antigen typing must be fully considered to avoid the occurrence of GVHD.

1.4. Bone and joint system diseases

The human osteoblasts have the ability to proliferate and differentiate. When the damage is not serious, the bone itself can undergo a certain degree of self-repair. For more severe bone and cartilage injuries, especially when there are a large number of bone defects, local blood supply, and oral and maxillofacial fractures that do not heal, stem cell transplantation still plays a very important role. From the source of bone and joint development, mesenchymal stem cells derived from mesoderm are the most widely used in bone and joint diseases. Mesenchymal stem cells can migrate to the site of injury and differentiate into osteoblasts and chondrocytes to repair bone damage. In osteoarthritis and sports injuries, stem cell therapy has been found to reduce pain, repair cartilage degradation, and promote motor function recovery. The mechanism of stem cell treatment of bone and joint diseases is multi-faceted, including paracrine function, improving microenvironment, promoting angiogenesis, replacement repair, etc. It is currently believed that the main role is to improve the local microenvironment of bone injury.

1.5. Eye diseases

The application of stem cell transplantation in ophthalmology is mainly to promote the repair of cornea and retina. There are a certain number of stem cells inside the eye tissue, mainly limbal stem cells (LSC), which is also a class of stem cells that are widely used in ophthalmology. It has a certain therapeutic effect on corneal injury and limbal stem cell deficiency, but it faces a limited source and immune rejection during allogeneic transplantation, which limits a large range of clinical applications. Fat or bone marrow-derived MSCs are another ideal cell type, and have certain therapeutic effects on glaucoma, retinal pigment degeneration, and macular atrophic damage combined with retinal yellow spots (Stargardt disease). Animal studies have found that MSCs can differentiate into photoreceptors and retinal pigment epithelial cells, secrete neurotrophic factors, and inhibit the apoptosis of optic nerve cells, and transplantation under the retina is more effective than intravitreal. Clinical studies have found that MSCs can migrate into the macular area of the retina and improve the patient's vision, but the effect almost disappears after 1 year. Considering that the cell type is not suitable for growth in the eye, it is only a short-term effect that occurs through the secretion of trophic factors. In addition: ESCs or i PSC-derived retinal pigment epithelial cells and oral mucosal epithelial cells can also be selected, and it has a therapeutic effect on patients with age-related macular degeneration and retinitis pigmentosa.

Because MSCs and HSCs have a wide range of sources, the preparation difficulty is relatively low, the safety is good, the paracrine and immunomodulatory effects are strong, so they are currently widely used. In addition to the diseases mentioned above, there are many diseases that may benefit from stem cell transplantation. Type 2 diabetes is essentially an autoimmune disease mediated by T cells. Therefore, the use of MSCs or HSCs can regulate immune function, inhibit T cell activation and inflammatory factor production, so as to relieve the symptoms of diabetes and reduce the amount of insulin. In addition, other diseases such as hepatitis, cirrhosis, burns, skin damage, systemic lupus erythematosus, rheumatoid arthritis, intestinal Crohn's disease, acute respiratory distress syndrome and other diseases have also been studied using mesenchymal stem cell therapy.

To ensure the success of stem cell therapy, we must first solve the problem of stem cell survival and migration after transplantation. Many studies have found that the stem cells transplanted into the body have a short survival time and cannot differentiate into target cells and function. Therefore, ensuring the homing, survival, differentiation and normal migration of transplanted stem cells is the key to effective treatment. There have been attempts to combine drugs (sodium ferulate, lithium valproate, erythropoietin), or related physical therapy (shock wave), or pre-treatment of stem cells (endothelial nitric oxide synthase) during the culture stage Enhancer, and embedding stem cells into biological materials (such as hydrogels, fabricated scaffolds) to increase the success rate of stem cell transplantation. For the problem of low cell differentiation efficiency in vivo, direct transplantation of totipotent stem cells should be avoided as far as possible, and high-purity tissue-specific precursor cells can be differentiated in vitro for transplantation, which also reduces the risk of tumorigenesis. Secondly, stem cells exist in many tissues and organs of the human body. Extracting and applying these stem cells is a good choice, but the problem is to obtain sufficient and effective stem cells. During the in vitro expansion process, the characteristics of stem cells may change to some extent, making them no longer suitable for repairing damaged tissues. Moreover, after the occurrence of the disease, the microenvironment of the lesion has undergone tremendous changes, which will also adversely affect the survival and migration of stem cells after transplantation. Finally, the standardization of stem cell preparation and transplantation, including the number and purity of stem cells, cell viability, route of administration, frequency, transplantation site, and the optimal time for treatment, all require careful evaluation and selection. It is important to establish a set of stem cell preparation and expansion standardized procedures for augmentation, storage and transplantation to achieve a stable treatment effect.

References

[1] Ferraro F,Celso CL,Scadden D. Adult stem cels and their niches[J].Adv Exp Med Biol,2010,695:155-168.

[2]  Ito Y,Nakamura S,Sugimoto N,et al. Turbulence activates platelet biogenesis to enable clinical scale ex vivo production[J]. Cell,2018,174(3):636-648.

[3] Regueiro A,Cuadrado-Godia E,Bueno-Beti C,et al. Mobilization of endothelial progenitor cells in acute cardiovascular events in the PROCELL study:time-course after acute myocardial infarction and stroke[J]. J Mol Cell Cardiol,2015,80:146-155.

[4] Bochon B,Kozubska M,Suryga?a G,et al. Mesenchymal stem cells-potential applications in kidney diseases[J]. Int J Mol Sci,2019,20(10):2462. 

[5]  Ming GL,Song H. Adult neurogenesis in the mammalian brain:significant answers and significant questions[J]. Neuron,2011,70(4):687-702.


  Report Entry
Sign in to follow this  
Followers 0


0 Comments


There are no comments to display.

Please sign in to comment

You will be able to leave a comment after signing in



Sign In Now