Adipose Tissue-Derived Stem Cells
Photo Credit: The Adipose Stem Cell Research Laboratory | University of Pittsburgh
Stem cell research is touted as the next tool through which medical breakthroughs will be achieved. Since 2004, millions of dollars in grants have been awarded to educate the public and fund stem cell research in California (CA), after a proposition was approved by voters to create the California Institute for Regenerative Medicine (CIRM). 1% of that funding, to date, has been set aside for urinary tract/kidney disease research [https://www.cirm.ca.gov/our-progress/stem-cell-research-funding-overview]. But stem cell research is controversial, right? Doesn’t it involve the use of embryonic stem cells which are derived from harvested embryos? Aren’t people worried that people will choose to terminate pregnancies for profit and that would be an ethical issue? No! – Not all stem cell research uses embryo-derived cells. Stem cells are found throughout the body in various adult tissues including bone marrow, which can be used to obtain stem cells, referred to as “adult stem cells”. These are the cells that your body produces naturally, that inhabit various tissues that need to be regenerated constantly: bone marrow (blood cells), adipose (fat) tissue, mesenchymal cells, or even the dental pulp of your teeth contain adult stem cells. Mesenchymal stem cells (MSCs) derived from the bone marrow or from within the vasculature within fat tissue [Zuk, P. A., 2001] can ultimately become bone, cartilage or fat cells. Research studies have shown that MSC’s can mature and incorporate into living lung, liver, heart [Li, J. H., 2008] and even the brain. Stem cells can also be harvested from muscle (a source that is easily accessed and available in large quantities). Although embryonic stem cells were initially favored as it was thought they were more flexible to become any kind of tissue, this has been shown to not be the case. Adult MSC’s have been shown to be just as efficient in developing into vascular cells, for instance [De Coppi, P., 2007].
Initial stem cell studies in experimental animal models have been useful in determining which tissues are good sources of stem cells and what sources are most effective for therapeutic development. Stem cells, not yet programmed with their ultimate function, are in a holding pattern but contain the potential to develop into mature functioning cells of a tissue; they are known as “undifferentiated”. They may ultimately become part of the skin or functioning muscle cells that contract — whatever the structure specific to the tissue to which they ultimately migrate and are conditioned to mature and replace old or damaged cells.
Antria, a company founded in Indiana by a urologist, in fact, has recently been given the go-ahead from the FDA for phase II clinical trials. They are testing a process to harvest a patient’s own fat cells using liposuction and inject them back into the skin [Wells, Randy 2015] to achieve a youthful appearance like plastic surgery without a scalpel. The advantages of harvesting cells from your own body (autologous transplantation) to provide treatment are multifold. The body is less likely to reject cells from your own body, since the immune system will not consider them foreign, thus increasing the likelihood of successful treatment. In addition, one does not risk the possibility of introducing potentially dangerous infectious agents, as has happened in the past, when infectious agents of unknown origin were injected along transfused blood or tissue transplants that had been donated and considered life-saving. Prior to the discovery of HIV and Hepatitis-C viruses, many people became inadvertently infected with these dangerous viruses when they received infected blood or tissues from anonymous donors.
How do researchers envision the use of stem cells to alleviate various diseases and/or malfunctions within the urinary tract, though? An excellent paper was recently published [Kim, J. H., 2013] that reviews the stem cell research literature for urologic application. Although still in their infancy, studies are currently evaluating the use of stem cells for bladder outlet obstruction (BOO) by alleviating urethral sphincter muscle control [Nishijima, S. et al., 2007], restored muscle contraction in a model which simulates the aging bladder [Chen S., 2012] or overactive bladder [Huang, Y.-C., 2010], gene therapy [Song, Y. S., 2012] using stem cells as carrier vehicles, neural stem cell reconstitution of spinal cord injuries [Hu, Y., 2012] and tissue-engineering new materials that may be more stable than mesh implants for treating pelvic organ prolapse and/or seeding stem cells onto a layer of small intestinal cells to partially regenerate a bladder [Nitta, M., et al. 2010].
Sounds like science fiction? The work to date has primarily been done by isolating and growing stem cells in a petri dish. The stem cells are later injected into an animal model (rats) with artificially-compromised bladders, which are later examined/tested for signs of improvement. However, there is a report of a small study of women with Stress Urinary Incontinence (SUI) in Europe, who were injected with muscle-derived stem cells [Mitterberger, G. M., 2008]. There are certainly many challenges and concerns related to the use of stem cells for treatment of diseases that need to be worked out. A primary concern is ensuring that the desired effect is achieved rather than uncontrolled growth (cancer). For bladder disease therapy, specifically, the exact growth conditions under which stem cells can be reliably directed to mature into bladder cells is still unknown. This is certainly an area of research to keep an eye on and as challenges are dealt with, could become a viable treatment option for patients with bladder disease.
References:
Chen S., H.-Y. Zhang, N. Zhang, et al. “Treatment for chronic ischaemia-induced bladder detrusor dysfunction using bone marrow mesenchymal stem cells: an experimental study,” International Journal of Molecular Medicine, 2012 29(3):416-422.
De Coppi, P., A. Callegari, A. Chiavegato et al., “Amniotic fluid and bone marrow derived mesenchymal stem cells can be converted to smooth muscle cells in the cry-injured rat bladder and prevent compensatory hypertrophy of surviving smooth muscle cells,” Journal of Urology 2007 177(1):369-376.
Hu, Y., L. M. Liao, Y. H. Ju, G. Fu, H. Y. Zhang, and H. X. Wu, “Intravenously transplanted bone marrow stromal cells promote recovery of lower urinary tract function in rats with complete spinal cord injury,” Spinal Cord 2012 50(3):202-207.
Huang, Y.-C., A. W. Shindel, H. Ning, et al, “Adipose derived stem cells ameliorate hyperlipidemia associated detrusor over-activity in a rat model,” 2010 Journal of Urology 183(3):1232-1240.
Kim, J. H., S.-R. Lee, Y. S. Song, H. J. Lee, “Stem Cell Therapy in Bladder Dysfunction: Where are we? And where do we have to go?,” BioMed Research International 2013:930713. doi: 10.1155/2013/930713. Epub 2013 Sep 16. PMCID: PMC3787556 PMID: 24151627
Li, J. H., N. Zhang and J. A. Wang, “Improved anti-apoptotic and anti-remodeling potency of bone marrow mesenchymal stem cells by anoxic preconditioning in diabetic cardiomyopathy,” Journal of Endocrinological Investigation, 2008 31(2):103-110.
Mitterberger, G. M., M. Pinggera, R. Marksteiner, et al, “Adult stem cell therapy of female stress urinary incontinence,” European Urology 2008 53(1)169-175.
Nishijima, S., K. Sugaya, M. Miyazato, et al. “Restoration of bladder contraction by bone marrow transplantation in rats with underactive bladder,” Biomedical Research 2007 28(5):275-280.
Nitta, M., T. Tamaki, K. Tono et al. “Reconstitution of experimental neurogenic bladder dysfunction using skeletal muscle-derived multipotent stem cells,” Transplantation 2010 89(9):1043-1049.
Song, Y. S., H. J. Lee, Doo, S. H., et al., “Mesenchymal stem cells overexpressing hepatocyte growth factor (HGF) inhibit collagen deposit and improve bladder function in rat model of bladder outlet obstruction,” Cell Transplant 2012 21(8):1641-1650.
Wells, Randy. The Indiana Gazette, 01/29/2015 https://www.indianagazette.com/news/indiana-news/fda-approves-next-phase-of-stem-cell-research,21395971/
Zuk, P. A., M. Zhu, H. Mizuno, et al., “Defining stem and progenitor cells within adipose tissue,” Stem Cells and Development 2001 7(2):211-228.
Read More Online:
“Key Research Events in Stem Cell Research”, Wikipedia. http://en.wikipedia.org/wiki/Stem_cell#Key_research_events
“Stem Cell Primer Basics”, California Institute for Regenerative Medicine. https://www.cirm.ca.gov/our-progress/stem-cell-basics