Over the past few years, data have accumulated showing the promise for cell-based therapies to help with the treatment of perianal Crohn’s disease. Specifically, stem cells appear to offer the opportunity to overcome several weaknesses associated with conventional therapies that have targeted perianal Crohn’s disease.
Based on these positive results, scientists and healthcare providers have become more adamant about understanding the broader role stem cells could play in the treatment of all inflammatory bowel disease. A new review published in Current Gastroenterology Reports discusses this specific issue and offers insights into the direction of stem cell research as it relates to inflammatory bowel disease.
The authors of this review discuss data from over a dozen clinical trials that have already been conducted on the impact of stem cell therapies in Crohn’s disease. Thus far, much of the success of regenerative medicine for the treatment of Crohn’s disease has been for the specific treatment of perianal Crohn’s disease, which occurs when the digestive and gastrointestinal inflammation associated with Crohn’s disease extends to the anal area.
Given the frequency with which the lining of the intestine is inflamed in inflammatory bowel disease, including both perianal Crohn’s disease and non-perianal Crohn’s disease, research efforts are focusing more and more on how stem cells may be able to combat this type of luminal disease. The authors put forth suggestions for the types of information that researchers should aim to obtain if we are to adequately treat intraluminal disease with regenerative medicine.
The potential of stem cells to address inflammatory bowel disease that has been demonstrated so far provides hope that this type of strategy will help not only patients with perianal Crohn’s disease but those with other forms of inflammatory bowel disease as well. More research should help to determine if and how these therapies can be deployed to help this patient population.
Reference: Lightner, A.L. (2019). Stem cell therapies for inflammatory bowel disease. Current Gastroenterology Reports, 21(4), 16.
For some men with prostate cancer, surgery to remove the prostate gland can be curative. The surgery to remove the entire prostate gland, called radical prostatectomy, can improve survival. If performed early, radical prostatectomy can prevent metastatic prostate cancer. While men who qualify for this surgery often jump at a chance to cure prostate cancer, radical prostatectomy comes with a price—it almost always causes erectile dysfunction.
Even under the best surgical conditions, most men experience at least temporary erectile dysfunction after radical prostatectomy. While some men can regain erectile function by using oral ED treatments, as many as 3 out of 5 men continue to have poor erections and/or difficulty with orgasm months to years after radical prostatectomy.
In an attempt to find a way to treat this serious issue, researchers in France conducted a clinical trial to test whether mononuclear cells treatment could improve erectile function in men who had undergone radical prostatectomy and developed erectile dysfunction (INSTIN, INtra-cavernous STem-cell INjection clinical trial, NCT01089387). Mononuclear cells are a type of stem cell that can become many other cells, including nerve or blood vessels cells. The researchers collected mononuclear cells from the bone marrow of affected men and injected these cells into the patient’s own penile tissue (i.e. autologous stem cell infusion). The researchers then followed the men for 6 to 12 months to track whether the mononuclear cells helped improve erectile function.
The first phase of the phase 1/2 clinical trial was designed to assess the safety of the treatment. No patients in the trial experienced any side effects from treatment. Likewise, prostate cancer did not return any of the men within one year after treatment (and perhaps longer, the men were only followed for one year at the time of the report).
Within six months of treatment, men treated with the bone marrow stem cells had a significantly better erectile function and satisfaction with sexual intercourse. While the benefit was still present after the 12 months, the erectile function was not quite as good as it was at six months after treatment. This suggests injections may need to be repeated every six months to maintain maximal benefit.
These results are incredibly encouraging for men with erectile dysfunction caused by radical prostatectomy. While future clinical trials should contain a control group and larger numbers of men, these phase 1/2 clinical trial results pave the way for such research. These findings also suggest men who have life-saving prostate cancer surgery may be able to regain erectile function after surgery through stem cell treatment.
Reference: Yiou, R. et al. (2017). Intracavernous Injections of Bone Marrow Mononucleated Cells for Postradical Prostatectomy Erectile Dysfunction: Final Results of the INSTIN Clinical Trial. European Urology Focus. 2017 Dec;3(6):643-645.
Osteoporosis is a disease in which bones become weak, brittle, and are prone to fracture. While osteoporosis is commonly considered a disease of low bone density, it is actually more complex and extensive than that. New bone is constantly formed and destroyed (resorbed) throughout life. In osteoporosis, however, the rate at which it is resorbed accelerates, while the rate at which it is formed slows down. In other words, bone is being destroyed faster than it can be formed. This process changes the size and shape of bones and alters its microarchitecture (i.e. the structure of bone on a microscopic level).
Without screening, most people will not know that they have osteoporosis until they have a bone fracture. Bones simply get weaker until some minor trauma causes one or more bones to break. Fortunately, efforts to screen for the disease (e.g. DXA/DEXA or bone density scans) have helped doctors diagnose cases of osteoporosis before the disease progresses to the point of bone fracture.
The main treatment for osteoporosis is a class of drugs called bisphosphonates. Bisphosphonates block the cells that resorb bone (osteoclasts) to allow the cells that form new bone (osteoblasts) to catch up. While bisphosphonates are effective, many patients experience severe GI side effects from these drugs including reflux, esophagitis, and ulcers, and cannot take them.
In an effort to find new ways to treat osteoporosis and help patients who cannot tolerate bisphosphonates, researchers are exploring the possibility of using stem cells to treat the disease. Ideally, one would take stem cells from patients, purify them, get the cells to multiply in the lab, and inject them back into patients with osteoporosis to help regrow bone. What has been unclear was whether a person with osteoporosis still has enough healthy stem cells to effectively regrow bone.
To test this, Dr. Jiang and colleagues collected stem cells from fat tissue of patients with osteoporosis (i.e. adipose-derived stem cells). The researchers took these stem cells and encouraged them to grow and multiply for 14 days. After the stem cells had proliferated, they injected the cells into mice and studied the effects on bone growth. After 4 weeks, the researchers saw evidence on X-ray scans that adipose-derived stem cells caused new bone growth.
These results demonstrate that even patients with osteoporosis still possess stem cells that can be used to treat their own osteoporosis. While the stem cells need to be treated in a laboratory setting for 14 days, it is potentially possible to use a patient’s own stem cells to regrow bone and treat their osteoporosis.
The next phase of research will be to conduct a clinical trial to show test whether autologous stem cell treatment (injecting a patient with their own stem cells) can regrow bone in humans. While those clinical studies will be critical in determining whether this approach is practical and effective for patients, this laboratory research is very promising.
Reference: Jiang, M. et al. (2014). Bone formation in adipose-derived stem cells isolated from elderly patients with osteoporosis: a preliminary study. Cell Biology International. 2014 Jan;38(1):97-105.
Frailty is a syndrome of weight-loss, exhaustion, weakness, slowness, and decreased physical activity. These features combine to make frail individuals more susceptible to physical, psychosocial, and cognitive impairments. Unfortunately, frailty is rather common among elderly individuals. In one study of over 44,000 elderly adults living in the community estimated the overall prevalence of frailty was 10.7%. While the risk of becoming frail increases with old age, frailty is not a normal part of aging. Instead, the syndrome of frailty is driven by biological processes such as inflammation and stem cell dysfunction.
No specific treatment can prevent or reverse frailty. Indeed, the goal of treatment is to maximize the patient’s functional capacity and overall health. The most widely accepted way to manage frailty is a multimodal and multidisciplinary approach. Frail individuals or those at risk for becoming frail are encouraged to participate in strength training and aerobic exercise to build up a cardiovascular reserve and physical fitness. At the same time, substantial efforts are devoted to helping patients consume enough calories to maintain lean muscle and support their immune function. As appetite diminishes, malnutrition can become an issue, so supplemental nutrition may be needed. Physicians can help patients by optimizing medical treatments and reducing the total number of medications prescribed (i.e. avoiding polypharmacy).
Despite these multimodal treatments, most frail patients tend to get worse over time. One hope of treatment is to slow the rate of decline; however, this is not always possible.
Since frailty is driven by stem cell dysfunction, a reasonable way to prevent or treat frailty could be to provide patients with healthy stem cells. Researchers recently conducted a randomized, double-blind, clinical trial in 30 elderly patients with frailty. Frail patients received an IV infusion of either human mesenchymal stem cells or placebo. The researchers then followed the patients for 6 months to assess the safety and efficacy of the stem cell treatment.
Stem cell treatment resulted in a rather remarkable set of benefits for frail patients. Compared to placebo, patients treated with stem cells performed significantly better on tests of physical strength and stamina. Stem cell-treated patients used calories more efficiently, which is a sign that they were more physically fit than those in the placebo group. Moreover, patients who received stem cells had better lung function at the end of the trial than those in the control group. Interestingly, women who received stem cell treatment reported a substantial increase in sexual quality of life compared to those in the placebo group. Lastly, no patients experienced any treatment-related serious adverse events.
When one considers how difficult it is to treat frailty or even alter its progressive decline, these results are remarkable. Stem cell treatment not only stopped the progression of frailty, but patients actually improved in several important measures including physical strength, physical endurance, lung function, and sexual quality of life. We anxiously await a pivotal clinical trial to confirm these results.
Reference: Tompkins, BA. (2017). Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial. The Journals of Gerontology, Series A, Biological Sciences and Medical Sciences. 2017 Oct 12;72(11):1513-1522.
You don’t need a microscope to recognize aging skin. Aging skin has fine lines and wrinkles; it sags because it has lost elasticity; it is discolored and blotchy. But if you did look at aging skin under a microscope, you would notice that it lacks collagen, elastin, and many other helpful proteins. There would be many old cells and a few young ones. Indeed, old skin looks different under a microscope than new skin, and it is these differences at the cellular level that causes the aging we see on people’s faces.
Fortunately, these cellular changes may not be a curse. Stem cell therapy may be able to replace the proteins that are lost during aging and replace old cells with newer, healthier cells. In short, stem cell therapy may be able to can rejuvenate facial skin and reverse the signs of aging.
The team of Korean stem cell researchers recently completed a study in which they collected mesenchymal stem cells from various sources and used them to rejuvenate human skin. The researchers collected stem cells from fat tissue (adipose), bone marrow, and umbilical cord samples. Umbilical cord tissue is tissue that is normally discarded after childbirth as medical waste. In the laboratory, the scientists then cleaned and purified each of these types of mesenchymal stem cells.
In laboratory studies, the researchers found that mesenchymal stem cells produced substantial amounts of skin rejuvenating factors including collagen type I, collagen type IV, fibronectin, and elastin. Interestingly, they found that umbilical cord mesenchymal stem cells produced a 100-fold greater amount of GDF-11 than adipose or bone marrow stem cells. This is important because GDF-11 is a cytokine that stimulates the production of collagen and elastin. GDF-11 also attracts human dermal fibroblasts (i.e. healthy skin cells) that then, in turn, produce their own collagen and elastin. These substances make skin healthy, elastic, vibrant, plump, and full.
Given the remarkable amounts of GDF-11 that umbilical cord-derived stem cells produced, the researchers decided to conduct a clinical trial to test the effect of these cells on aging skin. The scientists created a cream that contained the substances produced by the stem cells, including exosomes and beneficial proteins. The women who volunteered for the study applied the cream to their faces once per day. Within 2 to 4 weeks, the women had increased skin density (i.e. thickness/fullness) and substantially reduced wrinkles, especially around the eyes. Moreover, treatment with the stem cell-derived cream did not cause irritation, stinging, or any other adverse reaction.
This clinical study will need to be repeated in larger numbers of volunteers; however, the results are quite remarkable. Researchers were able to collect stem cells from umbilical cord tissue and prepare a cosmetic that reversed some of the signs of facial aging. Conveniently, this treatment did not require injections but could be applied topically. If future research confirms this work, treatment with a cosmetic/cosmeceutical made from umbilical cord stem cells could be a painless way to achieve facial skin rejuvenation.
Reference: Kim, YJ. (2018). Conditioned media from human umbilical cord blood-derived mesenchymal stem cells stimulate rejuvenation function in human skin. Biochemistry and Biophysics Reports. 2018 Oct 25;16:96-102.