Advances in Stem Cell Research
I originally published this blog on the CureScience Institute website and I thought I would share it with you. Stem cells are immature, undifferentiated cells which are capable of giving rise to indeterminately more cells of the same type. In addition, stem cells have the unique ability to divide and differentiate into various types of cells in the body. Stem cells are of vast importance in medical research and therapeutic applications due to their capability of dividing and specializing into numerous kinds of cells in the body [1]. These range from embryonic stem cells, induced pluripotent (capable of giving rise to different cell types) stem cells, and adult stem cells, each with its own set of properties and possible uses. For example, mesenchymal stem cells (MSCs) are a type of adult stem cell that can be isolated from various tissues in the body, including bone marrow, adipose tissue, and umbilical cord blood, and are the focus of many studies due to their ability to differentiate into more than one cell type, such as bone cells, cartilage cells, and muscle cells. Consequently, these adult stem cells collected from sources like bone marrow, adipose tissue, and umbilical cord blood are highly sought after for their potential use in regenerative medicine. Moreover, research shows that these MSCs may be able to modulate the immune system and contribute to tissue repair and regeneration through the secretion of beneficial bioactives including growth factors and cytokines [2].
Interestingly, human embryonic stem cells (hESCs) can be harvested from the inner cell mass of early-stage embryos and have the capability of both self-renewal as well as the capacity to diversify into any cell type found in the body. This unrestricted potential has made them a major area of investigation with regard to providing novel treatments for various disorders and injuries. In contrast, human mesenchymal stem cells (hMSCs) display more limited self-renewal qualities along with limited differentiation capabilities such as bone, cartilage and fat cells. Notwithstanding the foregoing, hMSCs offer various appealing features, like adjusting immune system modulation and tissue restoration support [3].
This article will examine a few of the ways in which stem cells are being developed to afford new medicinal treatments for various diseases.
Khalid Shah, MS, Ph.D., Vice Chair of Research at Brigham and Women’s Hospital (BWH), is also the Director of the Center for Stem Cell and Translational Immunotherapy at BWH and a faculty member at Harvard Stem Cell Institute in Boston. He sought to exploit cancer cells using gene engineering to create a treatment that eliminates tumors and encourages the immune system to fight primary tumors as well as potentially impede cancer. Their team formulated a simple concept to repurpose cancer cells, by leveraging gene engineering techniques, to create a means of eradiating tumor cells as well as stimulating the immune system to recognize and destroy the tumor[4].
Genetically engineered tumor cells that kill tumor cells as well as stimulate the immune system could potentially be used to treat cancer more effectively. In addition to avoiding the need to develop entirely new cell types for therapeutic purposes, repurposing tumor cells to become therapeutic agents is particularly intriguing. The capability of therapeutic tumor cells (ThTCs) in neutralizing glioblastoma tumors in mice is remarkable given the severity of this disease. As a precaution, a double kill-switch is used to ensure the safety of the approach. The use of bifunctional therapeutic tumor cells in cancer immunotherapy could potentially result in more effective treatments for solid tumors. A promising step towards clinical translation is the success of this approach in preclinical models.
In other developments, of the human population, approximately 7.4% are currently impacted by chronic lung disease, making respiratory disease a major cause of morbidity and mortality globally [5]. The large airways, small airways, and alveoli are subject to various forms of pathology resulting in a decrease in the functionality of the lung tissue. This will interfere with essential functions such as respiration, mucociliary clearance and immune cell production. Cystic fibrosis, primary ciliary dyskinesia, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and bronchiolitis obliterans are all respiratory disease disorders. Existing therapies targeting lung inflammation, bronchoconstriction, and fibrosis can only slow or control disease symptoms and progression [6]. No therapy currently exists to cure (reverse) the damage caused by these diseases. “Pro-regenerative” therapies are; however, being considered for respiratory diseases, which aim to boost lung tissue regeneration and repair. Exogenous stem cells (outside of the particular organ) can be introduced into the lung tissue or protected or stimulated to act as endogenous (inside the organ of interest) stem cells. Overall, the development of pro-regenerative therapies for respiratory diseases has the potential to offer a novel approach to treating these conditions, either alone or in combination with existing treatments. The mechanisms of lung regeneration need to be understood in greater detail before effective and safe regenerative therapies can be developed for clinical application [6]. Searching under the terms lung disease, pulmonary, stem cells, and United States in www.clinicaltrials.gov, approximately 153 trials were identified as recruiting, ongoing, terminated, and completed. Many of the trials utilized mesenchymal stem cells (alone or in combination with other drugs) as treatment modalities.
MSC’s have also been utilized in the treatment of degenerative disease associated with the joints and in the reconstruction of bones and cartilage. For example, It has long been clear that osteoprogenitor cells come from the bone marrow, and have the ability to form bone when introduced elsewhere [7,8]. This quality has been utilized in a minimally invasive approach to tackle non-union fractures.
Alzheimer’s Disease (AD) is associated with accumulation of Aβ proteins in selective regions of the brain and is a progressive neurodegenerative disease [9]. Stem cell therapy holds great promise for the treatment of Alzheimer’s disease; however, significant challenges still need to be overcome to translate this technology from preclinical studies to successful clinical applications. One of the major concerns is the risk of tumor formation, which has been reported in some preclinical studies using stem cells. Additionally, there is a need to develop more effective delivery systems and methods for controlling the proliferation and differentiation of stem cells. Another challenge is the heterogeneity of AD, which requires individualized treatments based on patient-specific characteristics. While there have been some promising results from animal and human studies, much more research is needed to fully understand the safety and efficacy of stem cell therapy for AD, and to develop effective treatment strategies that can benefit the diverse population of AD patients [9]. According to www.clinicaltrials.gov, using the search terms Alzheimer’s Disease, stem cells, and US, there are 13 clinical trials either ongoing or completed addressing the use of stem cells to treat neurological disorders like AD.
There is a myriad of disorders that are being addressed by stem cells, both in the laboratory and clinic, to exploit their properties to improve the overall human condition. As discussed, A stem cell can be manipulated to become a specific type of cell, such as a heart muscle cell, a blood cell or a nerve cell. If the patient has heart disease, the cells could be injected into the heart muscle. Injured heart muscle could then be repaired by healthy transplanted heart muscle cells. Adult bone marrow cells guided to become heart-like cells have already been shown to repair heart tissue, and further research is underway [10].
Notwithstanding all the good work that is ongoing, there are charlatan firms that tout stem cells as the ultimate therapy for many diseases. Most of these claims are untrue and have not been validated by the U.S. Food and Drug Administration. According to The Guardian In March 2015, David Vannoni was found guilty of perpetrating fraud and conspiracy for prescribing unproven stem cell therapies to patients at Stamina Foundation. Vannoni, who had no scientific or medical background, asserted that bone marrow cells could be converted to neural cells as a remedy for disorders such as Parkinson’s disease, muscular dystrophy or spinal muscular atrophy. Italian Medicines Agency endeavored to close the Brescia hospital facility in 2012, yet parents whose children were perishing due to terminal maladies went to court entreating stem cell treatments and managed to win. As a consequence, in 2013 the Italian government undertook a $3.9m clinical trial of the treatment. After years of campaigning and investigation by researchers, it was exposed that Vannoni’s assertions were erroneous. He was given a sentence of 22 months imprisonment, suspended on the condition that he abstain from curing patients [11].
When visiting websites that make claims of nearly miraculous cures using stem cells, people should check the site carefully for published authors, scientific articles purporting the claims that are published in an established peer-reviewed journal, and above all use common sense. The use of stem cells in various therapeutic modalities is an ongoing research and development issue that many believe will lead to life-saving results in the future.
Written By: Lawrence D. Jones, Ph.D.
Keywords: stem cells, mesenchymal, embryonic, gene engineering, lung disease, engineered tumor cells, msn
References:
1. https://www.mayoclinic.org/tests-procedures/bone-marrow-transplant/in-depth/stem-cells/art-20048117
4. Kok-Siong Chen, Clemens Reinshagen, Thijs A. Van Schaik, Filippo Rossignoli, Paulo Borges, Natalia Claire Mendonca, Reza Abdi, Brennan Simon, David A. Reardon, Hiroaki Wakimoto, Khalid Shah. Bifunctional cancer cell–based vaccine concomitantly drives direct tumor killing and antitumor immunity. Science Translational Medicine, 2023; 15 (677) DOI: 10.1126/scitranslmed.abo4778
5. GBD Chronic Respiratory Disease Collaborators (2020). Collaborators, Prevalence and attributable health burden of chronic respiratory diseases, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Respir. Med. 8, 585–596. 10.1016/S2213–2600(20)30105–3
6. Hynds RE. Exploiting the potential of lung stem cells to develop pro-regenerative therapies. Biol Open. 2022 Oct 15;11(10):bio059423. doi: 10.1242/bio.059423. Epub 2022 Oct 14. PMID: 36239242; PMCID: PMC9581519
7. Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med. 2013 Nov 15;45(11):e54. doi: 10.1038/emm.2013.94. PMID: 24232253; PMCID: PMC3849579.
8. Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV. Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol. 1966 Dec;16(3):381–90. PMID: 5336210.
9. Liu XY, Yang LP, Zhao L. Stem cell therapy for Alzheimer’s disease. World J Stem Cells. 2020 Aug 26;12(8):787–802. doi: 10.4252/wjsc.v12.i8.787. PMID: 32952859; PMCID: PMC7477654.
10. https://www.mayoclinic.org/tests-procedures/bone-marrow-transplant/in-depth/stem-cells/art-20048117#:~:text= These%20stem%20cells%20are%20manipulated,
injected%20into%20the%20heart%20muscle.
