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.
Autologous stem cell treatments offer several advantages over other forms of stem cell treatment. In autologous stem cell treatment, a patient’s own stem cells are retrieved, processed, and injected back into the patient’s body. There is no need for a stem cell donor, and the entire procedure can take place in the same medical office. Since the patient’s own cells are used for an autologous stem cell treatment, there is no risk of disease transmission from a donor (because there is no donor) and no risk of rejection (because they are the patient’s own stem cells).
Unfortunately, younger stem cells are better for regenerative medicine than older stem cells are. Moreover, older people have fewer stem cells that can be harvested than they did when they were younger. So while autologous stem cell treatment is still advantageous, it becomes more difficult to achieve as patients get older because their stem cells are fewer and less potent. Making matters worse, older stem cells compete against more youthful stem cells, making autologous stem cell treatments potentially even less effective in older patients.
Fortunately, stem cell researchers are coming up with ways to make the most out of the stem cells that older patients still have. They still take a sample of tissue, such as fat, and harvest the stem cells contained within it. However, instead of injecting all stem cells from the sample (both older and youthful stem cells), researchers select and use only youthful stem cells. Furthermore, they make the treatments even more effective by injecting other substances (e.g. extracellular matrix) that helps youthful stem cells survive, grow, and thrive.
To demonstrate the effectiveness of their approach, researchers collected mesenchymal stem cells from about a dozen older individuals aged 65 to 86 years old. They then assorted the stem cells into different groups, separating youthful from older stem cells. They then used special factors to help the youthful stem cells grow, increasing the numbers by an impressive 17,000 times. So while only 8% of stem cells produced by older individuals are “youthful,” this laboratory process increased those numbers to a point that they can be used for stem cell treatments—even stored for future use!
The next phase of the research will be to inject these youthful stem cells into older patients and assess their effectiveness. However, even these preliminary results are exciting, because they suggest that people of all ages can potentially benefit from autologous stem cell treatments, not just middle age and younger individuals.
Reference: Block, TJ et al. (2017). Restoring the quantity and quality of elderly human mesenchymal stem cells for autologous cell-based therapies. Stem Cell Research and Therapy. 2017 Oct 27;8(1):239.
Prostate cancer is quite common among men in the United States. The main treatment options for prostate cancer include:
- External beam radiation – Radiation is applied to the prostate gland through the skin (noninvasive)
- Brachytherapy – Radioactive pellets the size of grains of rice are placed within the prostate gland (invasive)
- Radical prostatectomy – The entire prostate gland and some surrounding tissue is removed
About one-quarter of all men with prostate cancer ultimately choose to have a radical prostatectomy. Unfortunately, this procedure often leaves men with chronic problems afterward, such as urinary incontinence (i.e., the inability to hold or control urine) and erectile dysfunction (i.e., the inability to achieve and maintain a penile erection suitable for sexual intercourse). Almost 90% of men who undergo radical prostatectomy to treat prostate cancer develop erectile dysfunction. Drugs and penile injections are not always effective in treating this type of erectile dysfunction. Consequently, as many as three-quarters of men must live with permanent erectile dysfunction. While prostate cancer is essentially cured after radical prostatectomy, affected men have substantially worse quality of life, which also negatively affects their sexual partners.
In an effort to combat this difficult problem, researchers conducted a Phase 1 clinical trial in which they took stem cells from the patient’s own fat tissue (autologous stem cells), purified them, and injected them into the penile tissue of radical prostatectomy patients with erectile dysfunction. Eight of the 17 men who volunteered for the clinical trial regained erectile function and were able to engage in sexual intercourse after just one stem cell injection.
Importantly, stem cell treatment was only effective for men who had not developed urinary incontinence. Eight of 11 men who still could control their urine after radical prostatectomy regained their ability to achieve and maintain erections. Conversely, no man with urinary incontinence after radical prostatectomy had erectile function restored.
The researchers noted that the stem cell treatment was very well tolerated by all men, and described the procedure as safe.
While larger clinical trials are needed to confirm these results, autologous stem cells taken from a patient’s own fat tissue were able to restore erectile function in most of the men treated. This research suggests that men who do not lose urinary function may benefit from this procedure. On the other hand, men who become incontinent after radical prostatectomy may not benefit from this particular stem cell therapy. Randomized, placebo-controlled clinical trials will help clarify this issue. In the meantime, these results are encouraging news to thousands of men who suffer from permanent erectile dysfunction as a result of their radical prostatectomies.
Reference: Haahr, MK et al. (2016). Safety and Potential Effect of a Single Intracavernous Injection of Autologous Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction Following Radical Prostatectomy: An Open-Label Phase I Clinical Trial. EBioMedicine. 2016 Jan 19;5:204-10.
Androgenetic alopecia is the medical term for pattern baldness. Pattern baldness can manifest in several ways such as a receding hairline, a bald spot in the crown of the head, and/or generalized thinning hair. Pattern baldness is the most common form of hair loss. Approximately 4 out of 5 men will experience some degree of androgenetic alopecia by the time they reach age 70. Androgenetic alopecia affects a substantial number of women as well. Pattern baldness is not lethal, but it can create substantial amounts of psychological suffering and greatly diminishes the quality of life for both men and women.
The two first-line treatments for androgenetic alopecia in men are finasteride or minoxidil. Finasteride is an oral medication, while minoxidil is topical, i.e. it is placed on this directly on the scalp. These baldness treatments are modestly effective in a certain percentage of men. Patients may also be treated with dutasteride, light therapy, platelet-rich therapy, or surgery. Minoxidil is the main form of treatment for women with androgenetic alopecia. If minoxidil fails to help regrow hair or stop the balding process, women may alternate treatments including spironolactone, finasteride, cyproterone acetate, or flutamide. As with male pattern baldness, female pattern baldness is somewhat resistant to treatment, leaving most women to cover their baldness with wigs or concealers.
One important observation about androgenetic alopecia is that while the number of hair follicle stem cells remains the same in people who are balding, the number of more actively proliferating progenitor cells drops dramatically. In other words, it is theoretically possible to treat androgenetic alopecia with hair follicle stem cells that contain actively proliferating progenitor cells.
Indeed, researchers recently tested this hypothesis in a group of 11 patients with androgenetic alopecia. The researchers collected a bit of tissue from each patient and then purified the sample to collect hair follicle stem cells with actively proliferating progenitor cells. The doctors then injected those stem cells into balding areas on the patients’ scalps. For comparison, some were treated with a placebo injection, i.e. saltwater.
Patients treated with hair follicle stem cells enjoyed a 29% increase in hair density over the treated area. by contrast. Patients treated with placebo had less than a 1% increase in her density over the same time period. The researchers also noticed that they were substantially more stem cells in and around hair follicles in balding areas.
The authors of this research concluded that isolated cells are capable of improving hair density in patients with androgenetic alopecia. While additional, larger studies are needed to confirm these results, the current study provides strong evidence that bald and balding patients may benefit from autologous stem cell treatment.
Reference: Gentile P. et al. (2017). Stem cells from human hair follicles: first mechanical isolation for immediate autologous clinical use in androgenetic alopecia and hair loss. Stem Cell Investigation. 2017 Jun 27;4:58.
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.
Much of the medical research and clinical applications of regenerative medicine have thus far focused on stem cells and their potential to repair damaged or diseased tissue that has not responded to conventional therapies. Though there has been a lot of evidence to suggest that the use of certain types of stem cells can be safe, experts have suggested that strategies for therapy that can avoid the use of living stem cells may provide an even better opportunity to slow the progression of various diseases.
Paracrine secretions have been shown to play a significant role in the ability of stem cells to improve disease conditions, and exosomes are a key element of these secretions. From a functional standpoint, exosomes enable stem cells to transfer their genetic information to other cells residing in the damaged tissue.
Because these exosomes are responsible for some of the critical benefits of stem cells, researchers have speculated that the use of exosomes rather than stem cells may provide specific advantages in some therapeutic contexts. A review in Stem Cells International has provided a comprehensive overview of what is known so far about the potential role of exosomes in regenerative medicine.
Exosomes are released from a wide variety of stem cell types and influence the functioning of nearby cells and tissues. The use of exosomes alone may offer better therapeutic results. Indeed, exosomes have shown particular promise in addressing otherwise incurable diseases.
In addition to developing our understanding of how exosomes can work to repair damaged tissue and improve functioning, new research efforts should also help to identify ways to overcome practical challenges associated with the use of exosomes. Isolating exosomes, for instance, can be time-consuming and require a large volume of cells. Though researchers are hopeful that exosomes will be able to help patients in new and innovative ways, more research is needed to determine the best way to apply exosomes in regenerative medicine.
Reference: Han, C. et al. (2016). Exosomes and their therapeutic potentials of stem cells. Stem Cells International, 1-11.