Biology:Clinical uses of mesenchymal stem cells

From HandWiki

Adult mesenchymal stem cells are being used by researchers in the fields of regenerative medicine and tissue engineering to artificially reconstruct human tissue which has been previously damaged. Mesenchymal stem cells are able to differentiate, or mature from a less specialized cell to a more specialized cell type, to replace damaged tissues in various organs.[1][2][3]

Isolation of mesenchymal stem cells

Obtaining mesenchymal stem cells from the bone marrow

In the research process of expanding the therapeutic uses of mesenchymal stem cells, they are grown in laboratories or grown using medication to stimulate new cell growth within the human body. In mesenchymal stem cell therapy, most of the cells are extracted from the adult patient's bone marrow [2][3] Mesenchymal stem cells can be obtained via a procedure called bone marrow aspiration. A needle is inserted into the back of the patients hip bone and cells are removed to be grown under controlled in vitro conditions in a lab. Over a course of two or three weeks, the cells will multiply and differentiate into specialized cells. The number of fully differentiated cells and their phenotype can be influenced in three ways. The first one is by varying the initial seed density in the culture medium. The second is by changing the conditions of the medium. The third is by the addition of additives such as proteins or growth hormones to the culture medium to promote growth. The mature cells are then harvested and injected back into the patient through local delivery or systemic infusion.

Isolation efficiency

Isolation of mesenchymal stem cells from the bone marrow requires an invasive procedure. Mesenchymal stem cells can also be isolated from birth-associated tissues such as the umbilical cord without the need for an invasive surgical procedure. Differences in isolation efficiency are attributed to the availability, condition, and age of the donor tissue. An issue related to culturing mesenchymal stem cells is the insufficient number of cells that can be produced.[1][3] During long-term culture, mesenchymal stem cells age, lose their ability to differentiate, and have a higher chance to undergo malignant transformation.[4][5]

Therapeutic properties

Mesenchymal stem cells possess many properties that are ideal for the treatment of inflammatory and degenerative diseases.[6][7] They can differentiate into many cell types including bone, fat, and muscle which allow them to treat a large range of disorders.[8][9] They possess natural abilities to detect changes in their environment, such as inflammation. They can then induce the release of bioactive agents and the formation of progenitor cells in response to these changes.[9] Mesenchymal stem cells have also been shown to travel to sites of inflammation far from the injection site.[7][10][11]

Mesenchymal stem cells can be easily extracted through well-established procedures such as bone marrow aspiration.[7] Also, transplanted mesenchymal stem cells pose little risk for rejection as they are derived from the patients own tissue, so are genetically identical, however graft versus host disease is a possibility, where the cells change enough while outside the patient's body that the immune system recognizes them as foreign and can attempt to reject them. This can lead to symptoms such as itchiness, sensitive/raw skin and shedding or dry skin. .[6]

Advantages over embryonic stem cells

Several different forms of stem cells have been identified and studied in the field of regenerative medicine. One of the most extensively studied stem cell types are embryonic stem cells, which possess many of the same therapeutic properties as mesenchymal stem cells, including the ability to self-regenerate and differentiate into a number of cell lineages.[8] Their therapeutic abilities have been demonstrated in a number of studies of autoimmunity and neurodegeneration in animal models.[8][7][10][12]

However, their therapeutic potential has been largely limited by several key factors.[7] Injected embryonic stem cells have been shown to increase the risk for tumor formation in the host patient.[8][7][12] Also, the host's immune system may reject injected embryonic stem cells and thus eliminate their therapeutic effects.[7] Finally, research has been largely limited due to the ethical issues that surround their controversial procurement from fertilized embryos.[8][12]

Safety concerns

Human mesenchymal stem cell therapy is limited due to variation in individual response to treatment and the high number of cells needed for treatment.[2] More long-term studies are needed to ensure the safety of mesenchymal stem cells. In previous studies which observed the safety of clinical mesenchymal stem cell use, no serious side effects were noted.[3] However, there have been some cases where there were both improvement and toxicity inflicted on the targeted organ, as well as cases where treatment of mesenchymal stem cells did not show improvement of function at all. In addition, there is a risk of tumorigenesis after stem cell transplantation due to the ability of stem cells to proliferate and resist apoptosis. Genetic mutations in stem cells as well as conditions at target tissue may result in formation of a cancerous tumor. Studies have shown that bone marrow mesenchymal stem cells can migrate to solid tumors and promote tumor growth in various cancer models [13][14][15][16] through the secretion of proangiogenic factors.

Treated disorders

Mesenchymal stem cells have been used to treat a variety of disorders including cardiovascular diseases, spinal cord injury, bone and cartilage repair, and autoimmune diseases.

Treatment for multiple sclerosis

A vast amount research has been conducted in recent years for the use of mesenchymal stem cells to treat multiple sclerosis.[17][18] This form of treatment for the disease has been tested in many studies of experimental allergic encephalomyelitis, the animal model of multiple sclerosis, and several published and on-going phase I and phase II human trials.[8][6][9][12]

Treatment requirements

Current treatments are unable to prevent the accumulation of irreversible damage to the central nervous system.[11] Patients with multiple sclerosis experience two major forms of damage, one from on-going autoimmune induced processes and the other to natural pair mechanisms.[6] Therefore, an ideal treatment must possess both immunomodulating properties to control irregular autoimmune responses and regenerative properties to stimulate natural repair mechanisms that can replace damaged cells.[8][6]

Therapeutic mechanisms

The exact therapeutic mechanisms of mesenchymal stem cells in the treatment of multiple sclerosis are still very much up to debate among stem cell researchers.[8][6][9] Some of the suggested mechanisms are immunomodulation, neuroprotection, and neuroregeneration.[6]

  • Immunomodulation
Mesenchymal stem cells can induce the release of bioactive agents such as cytokines that can inhibit autoimmune responses.[8][6] In patients with multiple sclerosis, autoreactive lymphocytes such as T and B cells cause damage to the central nervous system by attacking myelin proteins. Myelin proteins make up the myelin sheath that functions in protecting nerve axons, maintaining structural integrity, and enabling the efficient transmission of nerve impulses.[11] By suppressing the unregulated proliferation of T and B cells, mesenchymal stem cells can potentially minimize and control on-going damage to the central nervous system.[8][9][11]
Mesenchymal stem cells can also stimulate the maturation of antigen presenting cells.[6][9] Antigen presenting cells trigger the immune system to produce antibodies that can destroy potentially harmful agents.[6] This property allows mesenchymal stem cells to actively contribute to neutralizing harmful autoreactive T and B cells.[8]
  • Neuroprotection
Mesenchymal stem cells can promote neuroprotection in the central nervous systems which may prevent the progression of chronic disability.[11] The mechanisms include inhibiting apoptosis of healthy cells and preventing gliosis, the formation of a glial scar.[6][11] They can also stimulate local progenitor cells to produce replacement cells for rebuilding the myelin sheath.[6]
  • Neuroregeneration
The regenerative abilities of the central nervous system are greatly decreased in adults, impairing its ability to regenerate axons following injury.[11] In addition to this natural limitation, patients with multiple sclerosis exhibit an even greater decrease in neuroregeneration along with enhanced neurodegeneration.[8][11][17][18] They experience a significant decrease in the number of neural stem cells which produce progenitor cells necessary for normal maintenance and function.[6][9] Decreases in the neural stem cells results in severe damage to the ability of the central nervous system to repair itself.[9] This process results in the amplified neurodegeneration exhibited in patients with multiple sclerosis.[6][9]
Mesenchymal stem cells have the ability to stimulate neuroregeneration by differentiating into neural stem cells in response to inflammation. The neural stem cells can then promote the repair of damaged axons and create replacement cells for the damaged tissue.[11][19] Regeneration and repair of damaged axons has been shown to occur naturally and spontaneously in the central nervous system. This shows that it is an environment capable of unassisted, natural healing.[19] Mesenchymal stem cells contribute to this regenerative environment by releasing bioactive agents that inhibit apoptosis and thus create an ideal regenerative environment.[6]

Cardiovascular Diseases

Mesenchymal stem cells are able to alleviate heart fiber injury and prevent cardiac muscle cell death in mouse models of myocardial infarction, or heart attack, and prevent its further development.[20][21][22] They can migrate to areas of inflammation and decrease infarction and improve cardiac function.

Brain Disorders

Mesenchymal stem cells have the potential to treat brain strokes as well. They can secrete factors that stimulate the function of brain cells, leading to neuron formation, blood vessel formation, and improved synaptic plasticity. They can also differentiate into neurons and neural cells to replace damaged cells. Behavioral tests performed in mouse models demonstrated a return to normal brain function after treatment with mesenchymal stem cells.[23][24]

Liver Diseases

Mesenchymal stem cells can also regenerate and repair damaged liver cells. In mouse models of liver fibrosis, mesenchymal stem cells delivered to the liver were shown to improve liver function by reducing inflammation and necrosis and inducing hepatocyte regeneration.[25][26][27]

References

  1. ↑ 1.0 1.1 "Usage of Human Mesenchymal Stem Cells in Cell-based Therapy: Advantages and Disadvantages". Development & Reproduction 21 (1): 1–10. March 2017. doi:10.12717/DR.2017.21.1.001. PMID 28484739. 
  2. ↑ 2.0 2.1 2.2 "Mesenchymal Stem Cells Current Clinical Applications: A Systematic Review". Archives of Medical Research 52 (1): 93–101. January 2021. doi:10.1016/j.arcmed.2020.08.006. PMID 32977984. 
  3. ↑ 3.0 3.1 3.2 3.3 "The Pros and Cons of Mesenchymal Stem Cell-Based Therapies". Cell Transplantation 28 (7): 801–812. July 2019. doi:10.1177/0963689719837897. PMID 31018669. 
  4. ↑ "Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation". Cancer Research 69 (13): 5331–5339. July 2009. doi:10.1158/0008-5472.CAN-08-4630. PMID 19509230. 
  5. ↑ "Sarcoma derived from cultured mesenchymal stem cells". Stem Cells 25 (2): 371–379. February 2007. doi:10.1634/stemcells.2005-0620. PMID 17038675. 
  6. ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 6.14 "Bone marrow mesenchymal stem cell transplantation in patients with multiple sclerosis: a pilot study". Journal of Neuroimmunology 227 (1–2): 185–189. October 2010. doi:10.1016/j.jneuroim.2010.07.013. PMID 20728948. 
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 "Characterization of in vitro expanded bone marrow-derived mesenchymal stem cells from patients with multiple sclerosis". Multiple Sclerosis 16 (8): 909–918. August 2010. doi:10.1177/1352458510371959. PMID 20542920. 
  8. ↑ 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 8.10 8.11 "Immunomodulation and neuroprotection with mesenchymal bone marrow stem cells (MSCs): a proposed treatment for multiple sclerosis and other neuroimmunological/neurodegenerative diseases". Journal of the Neurological Sciences 265 (1–2): 131–135. February 2008. doi:10.1016/j.jns.2007.05.005. PMID 17610906. 
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 9.7 9.8 Caplan A. 2010. "Mesenchymal stem cells: the past, the present, the future". Cartilage. 1(1):6-9.
  10. ↑ 10.0 10.1 "Bone marrow-derived mesenchymal stem cells modulate BV2 microglia responses to lipopolysaccharide". International Immunopharmacology 10 (12): 1532–1540. December 2010. doi:10.1016/j.intimp.2010.09.001. PMID 20850581. 
  11. ↑ 11.0 11.1 11.2 11.3 11.4 11.5 11.6 11.7 11.8 "The promise of stem cell and regenerative therapies for multiple sclerosis". Journal of Autoimmunity 31 (3): 288–294. November 2008. doi:10.1016/j.jaut.2008.04.002. PMID 18504116. 
  12. ↑ 12.0 12.1 12.2 12.3 "Evaluation of bone marrow- and brain-derived neural stem cells in therapy of central nervous system autoimmunity". The American Journal of Pathology 177 (4): 1989–2001. October 2010. doi:10.2353/ajpath.2010.091203. PMID 20724590. 
  13. ↑ "Mesenchymal stromal cells promote tumor growth through the enhancement of neovascularization". Molecular Medicine 17 (7–8): 579–587. July 2011. doi:10.2119/molmed.2010.00157. PMID 21424106. 
  14. ↑ "Mesenchymal stem cells enhance growth and metastasis of colon cancer". International Journal of Cancer 127 (10): 2323–2333. November 2010. doi:10.1002/ijc.25440. PMID 20473928. 
  15. ↑ "Risk factors in the development of stem cell therapy". Journal of Translational Medicine 9 (1): 29. March 2011. doi:10.1186/1479-5876-9-29. PMID 21418664. 
  16. ↑ "Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth". Cancer Cell 19 (2): 257–272. February 2011. doi:10.1016/j.ccr.2011.01.020. PMID 21316604. 
  17. ↑ 17.0 17.1 "Decreased neural stem/progenitor cell proliferation in mice with chronic/nonremitting experimental autoimmune encephalomyelitis". Neuro-Signals 18 (1): 1–8. 2010. doi:10.1159/000242424. PMID 19786810. 
  18. ↑ 18.0 18.1 "Autologous haematopoietic stem-cell transplantation in multiple sclerosis: benefits and risks". Neurological Sciences 30 (Suppl 2): S175–S177. October 2009. doi:10.1007/s10072-009-0144-5. PMID 19882370. 
  19. ↑ 19.0 19.1 "Autologous mesenchymal bone marrow stem cells: practical considerations". Journal of the Neurological Sciences 265 (1–2): 111–115. February 2008. doi:10.1016/j.jns.2007.08.009. PMID 17904159. 
  20. ↑ "Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction". Nature Medicine 12 (4): 459–465. April 2006. doi:10.1038/nm1391. PMID 16582917. http://ousar.lib.okayama-u.ac.jp/files/public/1/10887/20160527185104695022/K003252.pdf. 
  21. ↑ "Myocardium-targeted transplantation of PHD2 shRNA-modified bone mesenchymal stem cells through ultrasound-targeted microbubble destruction protects the heart from acute myocardial infarction". Theranostics 10 (11): 4967–4982. 2020. doi:10.7150/thno.43233. PMID 32308762. 
  22. ↑ "Ultrasound‑targeted microbubble destruction‑mediated Galectin‑7‑siRNA promotes the homing of bone marrow mesenchymal stem cells to alleviate acute myocardial infarction in rats". International Journal of Molecular Medicine 47 (2): 677–687. February 2021. doi:10.3892/ijmm.2020.4830. PMID 33416139. 
  23. ↑ "Low intensity ultrasound targeted microbubble destruction assists MSCs delivery and improves neural function in brain ischaemic rats". Journal of Drug Targeting 28 (3): 320–329. March 2020. doi:10.1080/1061186X.2019.1656724. PMID 31429596. 
  24. ↑ "Ultrasound-targeted microbubble enhances migration and therapeutic efficacy of marrow mesenchymal stem cell on rat middle cerebral artery occlusion stroke model". Journal of Cellular Biochemistry 120 (3): 3315–3322. March 2019. doi:10.1002/jcb.27600. PMID 30537289. 
  25. ↑ "Ultrasound-targeted microbubble destruction optimized HGF-overexpressing bone marrow stem cells to repair fibrotic liver in rats". Stem Cell Research & Therapy 11 (1): 145. April 2020. doi:10.1186/s13287-020-01655-1. PMID 32245503. 
  26. ↑ "A combination of ultrasound-targeted microbubble destruction with transplantation of bone marrow mesenchymal stem cells promotes recovery of acute liver injury". Stem Cell Research & Therapy 9 (1): 356. December 2018. doi:10.1186/s13287-018-1098-4. PMID 30594241. 
  27. ↑ "Use of mesenchymal stem cells to treat liver fibrosis: current situation and future prospects". World Journal of Gastroenterology 21 (3): 742–758. January 2015. doi:10.3748/wjg.v21.i3.742. PMID 25624709. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:Clinical_uses_of_mesenchymal_stem_cells&oldid=3681184"