Mesenchymal Stem Cell (MSC) demonstrates the ability to differentiate into several tissue-forming cells such as bone, cartilage, fat, muscle, tendon, liver, kidney, heart, and even brain cells. (1, 2) They also have the ability to control or cure other cells and are able to reconstruct a coordinating function. Due to therapeutic effect, stem cells have been promoted in media and pain and regenerative clinics around the world. In this article, I will present the results of years of stem cell research and discuss its application in clinical practice.
Therapeutic effect of stem cells on organ function
Review of research provides evidence of the ability of stem cells to replace and repair damaged cells in internal organs. Studies have been gathering from around the world, including Europe, Asia, and the United States, on the function and effect of stem cells on living cells. The picture above presents the potential of each stem cell to differentiate to other cells when your body needs it. We all use stem cells all the time. When you are injured, your body will use stem cells to regenerate and create new muscle, ligament, or organ cells to replace these cells. An example for this biological reaction was seen in one of the studies published in The American Journal of Pathology. The study showed that administration of amniotic stem cells led to recovery from acute kidney injury. (3) The stem cells that were administrated in the research were converted to kidney cell and they facilitated the recovery of this organ. In similar way, your body uses stem cell to recover from any damage to joints, brain, and organ damage. Unfortunatly, we as we age, our stem cells age with us and it is estimated that they lose their ability to repair and build other cells. Currently, several medical centers, such as The Oregon Stem Cell Center at the Oregon Health and Science University (OHSU), are conducting studies with stem cell to discover the full therapeutic potential of Stem Cells.
Stem cells use in inflammatory condition and nerve damage
Stem cells demonstrated a safe and potent anti-inflammatory and immunosuppressive effect in human trials . Stem cell study that evaluated the potential of stem cells in regenerating and treating nerve injury concluded that stem cells have a great potential to improve the regeneration process. (5) A preliminary study evaluated the effect of local injections of stem cells in nine patients between the ages 27 and 80, who suffer from chronic nerve pain. The study showed a significant reduction in pain, from 7.5 (SD 1.58) to 4.3 (SD 3.28), six months after the stem cells procedure. These patients also reported this had reduced their need for the pain medication, gabapentin. (6)
Stem cells and joint health
Stem cells were also found to be beneficial in reducing joint pain and promoting healthy joints. A study published in the Journal of Transplantation evaluated the effect of stem cells injection on osteoarthritis patients. The study found that administration of stem cells exhibited rapid and progressive improvement in the quality of the cartilage in the knee of 11 out of 12 patients, as well as a reduction in pain. The study concluded that stem cell procedure is safe and effective in the treatment of osteoarthritis, an inflammatory and degenerative disease of the joint. (7)
Which type of stem cell should I use?
There are several types of stem cells in clinical use. A majority of clinics use stem cells that are harvested from your own tissue, such as bone or adipose (fat). Unfortunately, these stem cells might have been exposed to bacteria, viruses, and environmental toxins that are stored in fat tissues. According to the U.S. Environmental Protection Agency, over 80,000 chemicals are manufactured or processed in the U.S. and approximately 700 new industrial chemicals are introduced every year. A majority of the accumulating toxins in our body are stored in adipose (fat) tissue (8) and studies show that certain chemicals, such as persistent organic pollutant, can trigger dysfunction and inflammation. (9) Toxicity can affect every cell in our body. Since the effect of toxins and chemicals on stem cells is not clear, patients should utilize embryonic stem cells from the umbilical cord, rather than stem cells from fat tissues or bones.
Another reason to prefer embryonic stem cells over other forms of stem cells is the age of the stem cells. Unlike stem cells harvested from adipose (fat) tissues, embryonic stem cells are homogeneous and are not susceptible to the detrimental impact of age and disease. (10) In other words, our stem cells grow old with us. if the patient is 45 years old, the stem cells in the patient’s body would be 45 years old. A study published in 2017 on the effect of aging on stem cells concluded that: “there is increasing evidence that the aging process can have adverse effects on stem cells. As stem cells age, their renewal ability deteriorates and their ability to differentiate into the various cell types is altered.” (11)
Why use Stem Cells from Human amniotic tissue?
Human amniotic cells can differentiate into multiple cell lineages and thus have a great potential to become a cell source for clinical applications. Human amniotic tissue has been proven to contain unique forms of cells that can differentiate into many cell types. Amniotic tissue also contains collagen substrates, the full range of growth factors, amino acids, carbohydrates, cytokines, hyaluronic acid, fibroblasts, epithelial cells, extracellular matrix, micronized amniotic membrane, and other cells. The amniotic membrane is rich with the basic components necessary for tissue healing. It also provides an anti-microbial environment, anti-inflammatory characteristics, and anti-adhesion/anti-fibrotic capabilities, as noted in several studies. ,,,,
To remove the risk of graft-host reaction, the chorion, which has been shown to contain maternal antigens, has been removed. This maximizes the potential benefits of amniotic membrane in a variety of medical and surgical specialties. Additionally, the immunologically privileged nature of amniotic membrane has been shown in a multitude of research papers. With these capabilities and characteristics, this allograft may be used in a variety of clinical applications.
How to get maximum results from stem cell therapy?
To obtain the maximum results from stem cell therapy, a unique treatment protocol was developed to provide a continues stimulation to the stem cells. Several factors, such as nutrition, acupuncture, and herbs were found to be beneficial in stimulating the stem cells.
Several studies published in the last few years show that a combination of acupuncture or electro-acupuncture promotes the differentiation of stem cells and regeneration of nerve fibers in an injured spinal cord. (17, 18) Several studies on herbal medicine confirmed that certain biochemicals in herbs can stimulate and promote the growth of stem cells and might increase the effect of the treatment. (19) An example for the use of herbal medicine in combination with stem cell therapy is the use of the herbs curcumin and Radix Angelica sinesis.
Stem cells require an antioxidant mechanism to survive and repair cells. Curcumin has antioxidant and anti-inflammatory properties that can support the function of these cells. Studies showed that extraction of curcumin dried rhizome resulted in enhanced proliferation and differentiation of Stem Cells. (20) Radix Angelica sinesis, also referred to as Dang Gui or the ‘female ginseng,’ was found to have neuroprotective properties, and lead to a significantly higher percentage of cell differentiation from stem cells. (21) It is important to mention that some herbs, supplements, or medications might inhibit the activity of stem cells (19) and therefore, I recommend consulting with a professional provider who specialized in nutritional, herbal medicine, and acupuncture protocols to support the function of stem cells.
How long stem cells live?
Stem Cells have been proven to be viable and 'alive' and can clone themselves between 5 to 55 months. Here are some quotes from studies on the viability of Stem Cells by Dr. Muller-Sieburg, professor in Sanford-Burnham's Stem Cells and Regenerative Biology Program: (22)
"Some stem cells lasted five months and others more than three years."
"We have found that each stem cell is pre-programmed to self-renew only for a set amount of time that, in mice, ranges from a few months to several years."
Stem cells can differentiate to other cells. It is also important to remember that they also multiply themselves in a rapid pace. When you receive injection or IV full with 'young' stem cells, they start to multiple and differentiate according to your body needs. Clinical data from thousands of patients that received stem cells therapy have shown that stem cell keep 'repairing' different parts of the body for months after the initial administration.
*Link to the short article about length of life of Stem Cells: https://www.sciencedaily.com/releases/2011/03/110301111249.htm
What are Exosomes?
Exosomes are cell-derived vesicles that are present in many (and possibly all) eukaryotic fluids, including blood, urine, and cell cultures. They are liposomal vesicles (or ‘bubbles' of proteins, hormones and powerful regenerative and anti-inflammatory messengers) that are released from the stem cells.
The research shows positive results with using exosomes for cardiac and kidney function, reducing inflammation, and potentially beneficial results with cancer treatments. (23, 24) However, the studies that show nerve regeneration were done using stem cells. Although exosomes are now promoted as the first line of treatment in some clinics in the U.S., there is a major disadvantage to Exosomes; they are particles that are released from cells, such as stem cells, and are not a 'live' cell that can multiply. Therefore, they have a limited life cycle. Currently, their half-life in the body is unknown and therefore, it is unclear how long they are active.
In general, administration of stem cells has been found to be safe in humans and well tolerated without overt immune rejection. Since some chemical toxins are stored in the fat tissues and bone, it might beneficial to receive stem cells from a ‘cleaner’ source as birth tissue, amniotic membrane, and umbilical cord, which has a profound healing impact on tissue, inflammation, and fibrosis. Although not required, I recommend following a ‘Stem-Cell’ protocol of herbal, nutritional, and acupuncture for 3 to 6 months after the procedure to achieve optimum results. Please consult with a licensed and professional healthcare provider who is experienced with nutrition, herbs, and acupuncture and can provide you guidance after your stem cell procedure.
Pittenger MF, AM Mackay, SC Beck, RK Jaiswal, R Douglas, JD Mosca, MA Moorman, DW Simonetti, S Craig and DR Marshak. (1999). Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147. Retrieved from https://www.researchgate.net/profile/Mark_Moorman/publication/13188086_Multilineage_Potential_of_Adult_Human_Mesenchymal_Stem_Cells/links/09e4150a90c28d4180000000/Multilineage-Potential-of-Adult-Human-Mesenchymal-Stem-Cells.pdf
Alhadlaq A and JJ Mao. (2004). Mesenchymal stem cells: isolation and therapeutics. Stem Cells Dev 13:436–448. Retrieved from http://fac.ksu.edu.sa/sites/default/files/Mesenchymal_Stem_Cells_Isolation_and_Therapeutics-SCD-2004_0.pdf
Hauser PV, Fazio RD, Bruno S, et al. Stem Cells Derived from Human Amniotic Fluid Contribute to Acute Kidney Injury Recovery. The American Journal of Pathology. 2010;177(4):2011-2021. doi:10.2353/ajpath.2010.091245. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947295/
Bacigalupo A. (2004). Mesenchymal stem cells and haematopoietic stem cell transplantation. Best Pract Res Clin Haematol 17:387–399
Sayad Fathi S, Zaminy A. Stem cell therapy for nerve injury. World Journal of Stem Cells. 2017;9(9):144-151. doi:10.4252/wjsc.v9.i9.144. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620423/
Vickers, E. R., Karsten, E., Flood, J., & Lilischkis, R. (2014). A preliminary report on stem cell therapy for neuropathic pain in humans. Journal of Pain Research, 7, 255–263. http://doi.org/10.2147/JPR.S63361. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020887/
Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, Sentís J, Sánchez A, García-Sancho J. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation. 2013 Jun 27;95(12):1535-41. doi: 10.1097/TP.0b013e318291a2da.
Jackson E, Shoemaker R, Larian N, Cassis L. Adipose Tissue as a Site of Toxin Accumulation. Compr Physiol. 2017 Sep 12;7(4):1085-1135. doi: 10.1002/cphy.c160038.
La Merrill M, Emond C, Kim MJ, et al. Toxicological Function of Adipose Tissue: Focus on Persistent Organic Pollutants. Environmental Health Perspectives. 2013;121(2):162-169. doi:10.1289/ehp.1205485.
Stem cells, ageing and the quest for immortality. Rando TA. Nature. 2006 Jun 29; 441(7097):1080-6.
Ahmed ASI, Sheng MH, Wasnik S, Baylink DJ, Lau K-HW. Effect of aging on stem cells. World Journal of Experimental Medicine. 2017;7(1):1-10. doi:10.5493/wjem.v7.i1.1.
DeCoppi, P et al.’ Isolation of Amniotic Stem Cell Lines With Potential for Therapy. Nature Biotechnology 2007; Vol 24, No. 1:1274 – 1280
Toda, A, et al. The Potential of Amniotic Membrane/Amnion Derived Cells for Regeneration of Various Tissues. Journal of Pharmacological Sciences 2007; 105:215228
Huiren, T, et al., Implantation of amniotic Membrane to Reduce Post Laminectomy Epidural Adhesions. Eur Spine Journal, DOI10,1007/s00586-009-1013
Huiren, T, et al., Implantation of amniotic Membrane to Reduce Post Laminectomy Epidural Adhesions. Eur Spine Journal, DOI10,1007/s00586-009-1013
Young, R. Birth Tissue/Ankle Tendon Repair Study Released, Orthopedics This Week – Extremities, Wed, Sep 12th, 2012
Yan Q, Ruan J-W, Ding Y, Li W-J, Li Y, Zeng Y-S. Electro-acupuncture promotes differentiation of mesenchymal stem cells, regeneration of nerve fibers and partial functional recovery after spinal cord injury. Experimental and Toxicologic Pathology. 2011;63(1-2):151-156. doi:10.1016/j.etp.2009.11.002.
Ho T-J, Chan T-M, Ho L-I, et al. The Possible Role of Stem Cells in Acupuncture Treatment for Neurodegenerative Diseases: A Literature Review of Basic Studies. Cell Transplantation. 2014;23(4-5):559-566. doi:10.3727/096368914x678463. Retrieved from http://journals.sagepub.com/doi/pdf/10.3727/096368914X678463
Udalamaththa VL, Jayasinghe CD, Udagama PV. Potential role of herbal remedies in stem cell therapy: proliferation and differentiation of human mesenchymal stromal cells. Stem Cell Research & Therapy. 2016;7(1). doi:10.1186/s13287-016-0366-4. Retrieved from https://stemcellres.biomedcentral.com/articles/10.1186/s13287-016-0366-4
Widowati W, Sardjono CT, Wijaya L, Laksmitawati DR, Sandra F. Extract of Curcuma longa L. and (-)-epigallo catechin-3-gallate enhanced proliferation of adipose tissue-derived mesenchymal stem cells (AD-MSCs) and differentiation of AD-MSCs into endothelial progenitor cells. J US China Med Sci. 2012;9(1):22–9.
Wang Q, Zhou L, Guo Y, Liu G, Cheng J, Yu H. Differentiation of human adipose-derived stem cells into neuron-like cells by Radix Angelicae Sinensis. Neural Regen Res. 2013;8(35):3353–8.
Sieburg HB, Rezner BD, Muller-Sieburg CE. Predicting clonal self-renewal and extinction of hematopoietic stem cells. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(11):4370-4375. doi:10.1073/pnas.1011414108. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060234/
Barile L, Milano G, Vassalli G. Beneficial effects of exosomes secreted by cardiac-derived progenitor cells and other cell types in myocardial ischemia. Stem Cell Investigation. 2017;4:93. doi:10.21037/sci.2017.11.06.
De Toro J, Herschlik L, Waldner C, Mongini C. Emerging Roles of Exosomes in Normal and Pathological Conditions: New Insights for Diagnosis and Therapeutic Applications. Frontiers in Immunology. 2015;6:203. doi:10.3389/fimmu.2015.00203.