Minimally-invasive stem cell therapy for stress urinary incontinence may provide an effective nonsurgical treatment for this common condition. Clinical trials of periurethral stem cell injection have been underway and basic science research has demonstrated the efficacy of both local and systemic stem cell therapies. Results differ as to whether stem cells have a therapeutic effect by differentiating into permanent, functional tissues, or whether they exert benefits through a transient presence and the secretion of regenerative factors. This review explores the fate of therapeutic stem cells for stress urinary incontinence and how this may relate to their mechanism of action.
Urinary incontinence afflicts up to 1 in 2 women.1 It poses significant economic and quality of life burdens, with over $32 billion annual U.S. dollars spent managing it.2 Stress urinary incontinence (SUI) impacts up to 1 in 4 women and accounts for over $12 billion annual U.S. dollars in health care costs.1 Incontinence imparts major psychosocial burdens on those afflicted by it, and places women at risk for other debilitating conditions, including depression, anxiety, low self-esteem, social isolation, infection, pain, and sexual dysfunction.3 Therefore, a clear need to develop cost-effective, durable, and minimally invasive treatment for the condition exists.
Some patients with SUI effectively respond to conservative treatment, including pelvic floor physical therapy, biofeedback, pelvic floor electrical stimulation, or continence devices, such as pessaries.4, 5 Several surgical and transurethral treatments are also available, including peri-urethral bulking injections and sub-urethral slings, which are the gold standard therapy for the condition.6 Slings offer the highest long-term cure rate for SUI, but like any surgery, are not without complications, which include sling erosion, urinary retention, bladder perforation, wound issues, and pain.7 Moreover, reports of complications involving vaginal mesh, while not pertaining to mid-urethral slings, have negatively swayed public opinion about such procedures.8 To date, besides conservative treatments, injectable therapies used to coapt the urethral lumen remain the least invasive SUI treatments providing some clinical benefit. These interventions produce no visible scars, but have largely fallen from clinical favor due to limited durability and efficacy.9
The utilization of stem cells and other progenitor cells as injectable agents, via a similar approach as bulking agents, present potential alternate therapies. Stem cells are unique due to their ability to proliferate, self-renew, and produce a population of differentiated progeny, making them a promising therapy in the field of regenerative medicine. To date, stem cells have been classified into four main categories. Embryonic stem cells (ESCs) derived from human blastocysts represent the most undifferentiated form, possessing the ability to differentiate into any human cell type.10 Theoretically, they provide the greatest therapeutic potential but their use is restricted by ethical concerns, as well as potential allogenicity and tumor oncogenesis.11 Amniotic fluid-derived stem cells (AFSCs) are a second form. This heterogeneous cell population is isolated from the amniotic fluid or placental membrane of a developing fetus, but their proliferation potential is only intermediate along the stem cell spectrum. Like ESCs, AFSCs can differentiate into many different cell lineages, but they are felt to possess lower tumorigenicity.12 A third form are differentiated, somatic cells that are “reprogrammed” into pluripotent cells.13 These induced pluripotent stem cells (IPSCs) possess similar differentiation potential to ESCs but preclude the necessity of an embryo. The utility of IPSCs in regenerative urology requires further investigation. Lastly, adult stem cells (ASCs) represent the most well understood type. These are tissue-specific progenitor cells, which are the most limited on the spectrum of differentiation.14 Mesenchymal stem cells (MSCs) are a subset of ASCs that can be isolated from bone marrow and induced to differentiate into various cell lineages. Recently, alternative sources of ASCs, such as muscle-derived stem cells (MDSCs) and adipose-derived stem cells (ADSCs) have been obtained with less invasive techniques compared to MSCs.15
In the pre-clinical setting, a variety of SUI models exist for investigating pathophysiology and treatment.19, 20 Leak point pressure (LPP), a measure of urethral resistance to leakage, determined by measuring bladder pressure at the time of leak, is a frequently utilized surrogate for SUI. Methods to decrease urethral resistance in order to elicit SUI are numerous and include direct urethral injury, urethrolysis, pudendal nerve injury, and vaginal distension.21–26 Bladder pressure can be increased to induce leakage using direct bladder compression, sneeze testing, or direct infusion using a suprapubic catheter.26–28 Additional assessments of these models include measurement of urethral closure pressure, testing of EUS function via electromyography (EMG), and histological studies of the EUS investigating muscle content and organization.19
This review addresses various applications of stem cells and progenitor cells to SUI, with a focus on recent developments in the field. The article also gives specific consideration to the mechanisms of therapeutic benefit from such cells, as well as implications for future studies and clinical applications. Commentary on the economic aspects of regenerative therapy for SUI is also included.
For the entire article / clinical trial, please click on the link below:
It’s been about half a century since the first transplant of bone marrow from a donor to a recipient was completed. Since then, bone marrow transplantation has become an integral part of care for many patients with persistent leukemia, lymphoma, multiple myeloma and other blood cancers, as well as noncancerous blood disorders such as sickle cell disease. Specifically, we are transplanting stem cells — nascent cells with the capacity to mature into functioning blood and immune system cells — from a matched or partially matched donor into the body of a patient whose own blood-forming system has been destroyed with toxic medication to make way for a healthy new system to grow and develop.
In recent years, however, our field has expanded to include other treatments that work in similar ways as bone marrow transplantation. They are collectively known as “cellular therapies” because they do one of three things: provide healthy new cells to replace diseased cells, release an influx of specially modified immune cells to teach the body’s immune cells how to fight disease, or provide cells that connect immune cells with cancer cells they are designed to kill. Study after study has demonstrated how these approaches are extending patients’ lives. This progression of therapies is reflected in bone marrow transplant services around the country, many of which — including our own at Hackensack University Medical Center — now include the words “cellular therapy” in their names.
It is an exciting time for those of us in the stem cell transplantation and cellular therapy field. For years, we have concentrated on improving the outcomes of stem cell transplants. We have significantly improved techniques to reduce the risk of graft-versus-host disease, a potentially serious complication of transplantation that occurs when immune cells from the donor identify the tissues of the recipient as foreign and attack them, causing a host of inflammatory symptoms. We have learned which medications to give to prevent post-transplant infections such as cytomegalovirus, a common virus that can be damaging in people with compromised immune systems. We are using stem cells from umbilical cord blood to perform more transplants in adult patients. And we have matched more patients with donors by learning how to perform “haploidentical” transplants, where the patient receives a transplant from someone who is partially matched immunologically. These advances are making stem cell transplantation a safer and more effective treatment option for more patients who need them.
But where we are really seeing a revolution in care is the field of cellular therapy — particularly CAR T-cell immunotherapy. Cancer cells have found ways to escape being detected and destroyed by immune cells. Immunotherapies work by helping the immune system find and kill cancer cells.
With CAR T-cell therapy, immune cells called T cells are removed from the patient, genetically modified in a lab to recognize and attach to certain targets on cancer cells, grown to larger quantities (hundreds of millions), and returned to the patient. There, the modified T cells can find, bind to and kill cancer cells. The treatment is given intravenously. Long after the patient goes home, however, his or her newly educated immune cells continue to detect and destroy cancer cells, which is why this treatment is often referred to as a “living therapy.”
CAR T-cell therapies are typically administered in bone marrow transplantation units, and for good reason: Patients receive chemotherapy beforehand, which reduces the immune response. The treatment itself can cause immunologic side effects which, albeit temporary, can be severe — including high fever, body aches and chills. The administration of CAR T-cell therapies requires round-the-clock care from a specially trained and credentialed team. As bone marrow transplant specialists, our experience and knowledge of immunology enable us to recognize and manage the inflammatory complications that may result.
Current CAR T-cell therapies are FDA-approved for the treatment of recurrent or persistent diffuse B-cell lymphoma, follicular lymphoma, multiple myeloma and mantle cell lymphoma (which is a very aggressive and challenging cancer) in adults, as well as acute lymphoblastic leukemia in children and young adults up to age 25. We are intrigued by other innovative cellular therapies under study in clinical trials, such as natural killer (NK) cells and tumor-infiltrating lymphocytes (TILs). These treatments are made from a patient’s own tumor tissue, so it has already been exposed to the patient’s own immune system. Immune cells within a tumor, which on their own were unable to kill the cancer, are isolated from tumor tissue removed during surgery, modified and multiplied in a lab, and returned to the patient with other medications to boost the immune response against cancer.
Not only is the technology getting better, but the types of tumors we are treating is broadening. New CAR T-cell therapies, NK and TIL treatments, and another approach that combines CAR T-cell and NK therapies may broaden the application of these “living therapies” to patients with solid tumors, including melanoma, breast cancer and pancreatic cancer. We’re also looking at combining cellular immunotherapies with stem cell transplantation to augment the anticancer immune response even further.
Cellular therapies are truly game-changers in cancer care. It has been inspirational for us as bone marrow transplant professionals to be part of their development. What we’re witnessing now is just the tip of the iceberg. We’re only getting better at identifying the best immune cells and engineering them in the best fashion to harness the immune system in the most effective way. Discovery is exponential and the field of immunotherapy is growing at warp speed. It’s not impossible to think that we’re going to be curing cancer.
Michele Donato, MD, is chief of the Adult Stem Cell Transplantation and Cellular Therapy Program at John Theurer Cancer Center, Hackensack University Medical Center.
For the entire article, please click on the link below:
In order to understand where cytokines and growth factors come from, we need to take a closer look at stem cells and how they carry out their functions.
Most of us know stem cells can differentiate to build new cells and tissue, but another role of stem cells is to orchestrate the action of other cells in the body, including the body’s natural healing and regeneration response. To carry out these actions, stem cells communicate by producing and releasing proteins called cytokines and growth factors. Controlled release of these cytokines and growth factors by stem cells will activate the biochemical pathways in adjacent cells and therefore command and control essential processes in the body. All cytokines and growth factors bind to specific receptors on cell membranes, stimulating the cells to carry out a precise and intricate response, thus giving the cell its ‘directions’. The types of cytokines and growth factors number in the thousands, each with its specific action. For skin renewal, these would include Epidermal Growth Factor (EGF), Vascular Endothelial Growth Factor (VEGF) and Transforming Growth Factor (TGF) amongst others. It’s important to note that no single growth factor determines the outcome within the cells. It’s the unique mix of peptides in specific proportions designed by nature that triggers our skin to repair and grow.
For more information on how Stem Cell Therapy and Plasma Rich Platelets (PRP) can help you look younger, please visit Miami Stem Cell www.stemcellmia.com
Clinical trial led by Thomas Jefferson University Hospital paves the way for innovative topical treatment
PHILADELPHIA – A minimally invasive treatment for individuals suffering from loss of smell and taste could become a reality. Led by Thomas Jefferson University Hospital otolaryngologist Dr. David Rosen, a team of physicians and researchers have developed a first-of-its-kind topical platelet-rich plasma treatment. Preliminary results from an ongoing clinical trial show promise in restoring patients’ sense of smell and taste.
Smell and taste disturbances known as anosmia and parosmia have grown in awareness in recent years since it is a common symptom of COVID-19. While the symptoms typically resolve for most individuals, up to 1.5 million people in the United States continue to experience long-term distortion of the sense of smell and taste.
Platelet-rich plasma (PRP) is a common restorative therapy used to regenerate cells, heal tissue, and address an array of medical conditions from healing injured muscles and tendons to increasing hair growth and reducing the appearance of scars. Animal studies have shown that PRP helps regenerate the olfactory epithelium, which may be the site affected in COVID-19 induced olfactory dysfunction (OD). As smell and taste are closely interrelated, improved sense of smell can help with sense of taste as well. Until now, PRP has been used as a nasal injectable in several small clinical trials for smell loss. Although the results were promising, nasal injections can be uncomfortable and invasive for patients.
“I’ve dedicated over two decades to helping patients recover from the loss of taste and smell,” said Dr. David Rosen, MD, Otolaryngologist, Thomas Jefferson University Hospital. “It was very important to me and our team to explore less invasive options as this issue has become increasingly prevalent due to COVID-19. The results of phase I of the clinical trial have been promising and we are looking forward to phase II to further improve the treatment.”
The new topical PRP treatment consists of monthly applications for a minimum of three months. A recent phase I clinical trial of eight patients who had at least six months of olfactory disturbance has shown preliminary success with 50 percent of participants experiencing clinically significant improvements in smell and taste. While phase I only consisted of eight patients, it is the largest pilot study to date for the use of PRP in treatment of OD and the first study to develop methods for topical delivery in human subjects. The new treatment has also been provided to dozens of additional patients independent of the phase I clinical trial with promising results.
A planned phase II study aims to exclusively look at patients who developed long term olfactory disturbance following recovery from COVID-19 infection. This will help the research team better understand patient variables and the number of treatments required to maintain sustainable improvements in smell and taste.
Stem cells have the potential to treat a wide range of diseases. Here, discover why these cells are such a powerful tool for treating disease—and what hurdles experts face before new therapies reach patients.
How can stem cells treat disease?
When most people think about about stem cells treating disease they think of a stem cell transplant.
In a stem cell transplant, stem cells are first specialized into the necessary adult cell type. Then, those mature cells replace tissue that is damaged by disease or injury. This type of treatment could be used to:
- Replace neurons damaged by spinal cord injury, stroke, Alzheimer’s disease, Parkinson’s disease or other neurological problems;
- Produce insulin that could treat people with diabetes or cartilage to repair damage caused by arthritis; or
- Replace virtually any tissue or organ that is injured or diseased.
But stem cell-based therapies can do much more.
- Studying how stem cells develop into heart muscle cells could provide clues about how we could induce heart muscle to repair itself after a heart attack.
- The cells could be used to study disease, identify new drugs, or screen drugs for toxic side effects.
Any of these would have a significant impact on human health without transplanting a single cell.
What diseases could be treated by stem cell research?
In theory, there’s no limit to the types of diseases that could be treated with stem cell research. Given that researchers may be able to study all cell types they have the potential to make breakthroughs in any disease.
How can I learn more about CIRM-funded stem cell research in a particular disease?
CIRM has created disease pages for many of the major diseases being targeted by stem cell scientists. You can find those disease pages here.
You can also sort our complete list of CIRM awards to see what we’ve funded in different disease areas.
What cell therapies are available right now?
While there are a growing number of potential therapies being tested in clinical trials there are only a few stem cell therapies that have so far been approved by the FDA. Two therapies that CIRM provided early funding for have been approved. Those are:
- Fedratinib, approved by the FDA in August 2019 as a first line therapy for myelofibrosis (scarring of the bone marrow)
- Glasdegib, approved in November 2016 as a combination therapy with low dose are-C for patients 75 years of age and older with acute myelogenous leukemia
Right now the most commonly used stem cell-based therapy is bone marrow transplantation. Blood-forming stem cells in the bone marrow were the first stem cells to be identified and were the first to be used in the clinic. This life-saving technique has helped thousands people worldwide who had been suffering from blood cancers, such as leukemia.
In addition to their current use in cancer treatments, research suggests that bone marrow transplants will be useful in treating autoimmune diseases and in helping people tolerate transplanted organs.
Other therapies based on adult stem cells are currently in clinical trials. Until those trials are complete we won’t know which type of stem cell is most effective in treating different diseases.
To find out more, please click on the link below:
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. COPD results from chronic inflammation of the lungs. Current treatments, including physical and chemical therapies, provide limited results. Stem cells, particularly mesenchymal stem cells (MSCs), are used to treat COPD. Here, we evaluated the safety and efficacy of umbilical cord-derived (UC)-MSCs for treating COPD.
To read the entire clinical trial, please click on the link below:
Allogeneic umbilical cord-derived mesenchymal stem cell transplantation for treating chronic obstructive pulmonary disease: a pilot clinical study (nih.gov)