Tissue engineering and regenerative medicine offer future patients greater options for treatment and cure of a wide array of urologic conditions, and controversies surrounding the sources of stem cells as well as their use have fueled increased research.
Here are highlights from the latest research:
ISOLATION OF HUMAN SPERMATOGONIAL STEM CELLS FROM TESTICULAR PARENCHYMA AND DIFFERENTIATION TOWARDS DIFFERENT TISSUES OF THE THREE HUMAN GERM LAYERS
Researchers in Tuebingen, Germany, investigated the possibility of isolating stem cells from human testicular parenchyma and whether those cells could them be differentiated into the different tissues of the three human germ layers: mesoderm, endoderm and ectoderm. Tissues were collected from orchiectomy specimens and cultured according to protocols specific to particular differentiation. The resulting “precurser cells” were then transplanted in utero in adult nude mice to test potency.
The study shows positive results, as the cells differentiated spontaneously into derivatives of all three primary germ layers, indicating that spermatogonial stem cells derived from adult testicular parenchyma could be a promising tool in reconstructive urology.
TISSUE-ENGINEERED AUTOLOGOUS BLADDERS FOR PATIENTS NEEDING CYSTOPLASTY
Cystoplasty using gastrointestinal segments is a common treatment for patients with end-stage bladder disease. However, researchers from Wake Forest University and Children’s Hospital Boston have reported viable results with engineered bladder tissue in a small group of patients with myelomeningocele (a type of spina bifida).
Using the patient’s own bladder tissue (obtained from biopsy), researchers grew urothelial and muscle cells and seeded them on collagen-based, bladder-shaped scaffolds. The bladder constructs were then used for reconstruction and implanted, some with an omental wrap. Overall follow up (ranging from 22 to 61 months, mean 46 months) showed a prompt return of bowel function, preserved renal function, normal mucus production and no urinary calculi. Results were best in those patients where implantation included an omental wrap.
IN-VIVO DIFFERENTIATION OF AUTOLOGOUS ADIPOSE TISSUE DERIVED STEM CELLS INTO UROLOGIC TISSUES
Human fatty tissue has been shown to be a viable, pluripotent source for stem cells that can be differentiated into a variety of cell lineages, including bone, muscle and neural cell types. San Francisco researchers investigated whether autologous adipose-derived stem cells could be differentiated into urologic tissues that could be used for reconstructive purposes.
Investigators harvested paragonadal adipose tissue from rat specimens and processed the tissue to yield the stem cells, which were then suspended in a phosphate-buffered solution (PBS) and injected into the bladder and proximal urethra of 16 Sprague-Dawley rats. A control group of 16 animals received PBS injection alone. Results showed that the cells differentiated into smooth and striated muscle, vasular and adipose tissues. Histologic evidence from this study suggests that fatty tissue may be an easily accessible source of stem cells that could be differentiated into urothelium, smooth muscle and other support tissue.
A NOVEL CELL SOURCE FOR UROLOGIC TISSUE RECONSTRUCTION
Tissue biopsy is the most common form of cell harvest necessary to obtain cells for expansion in tissue engineering and regenerative medicine. Researchers at Wake Forest University explored whether cells in human urine possess characteristics necessary for this application. The two most common tissue types used in urologic reconstruction are urothelial and smooth muscle progenitor cells.
Urine samples were obtained from nine healthy male donors and cells were isolated, expanded and characterized with cell-specific surface markers. After being seeded on collagen-based matrices in vitro, the tissues were implanted subcutaneously into athymic mice. The implanted cells formed multilayered tissue structures in vivo, and maintained their phenotypic and functional cellular characteristics, suggesting that urine may ultimately be a valuable source for cell harvest for urinary tract tissue reconstruction.
UNIVERSITY OF TORONTO CLINICAL TRIAL OF MUSCLE-DERIVED CELL INJECTION IN WOMEN WITH STRESS URINARY INCONTINENCE
Research into the use of muscle-derived stem cells to treat stress urinary incontinence has been ongoing. Researchers from the University of Pittsburgh and the University of Toronto report completed clinical results of the first North American clinical trial using autologous muscle-derived stem cells to treat stress urinary incontinence.
Using a needle biopsy technique, skeletal muscle tissue was harvested, stem cells isolated and expanded in vitro, and then implanted in patients using a transurethral or periurethral technique. No adverse events or safety issues were identified in the population.
FIBROBLASTS AND ADIPOSE-DERIVED STEM CELLS IN THE TREATMENT OF STRESS URINARY INCONTINENCE: COMPARISON OF FUNCTIONAL OUTCOMES
Improving urethral function has been an elusive target for researchers seeking viable treatments for stress urinary incontinence (SUI). However, Los Angeles researchers suggest that adipose-derived pluripotent cells may be a viable means to treat SUI and also improve urethral function.
Using human cells obtained from liposuction specimens, investigators differenciated stem cells into smooth muscle, seeded the cells on carrier matrices and injected them into the proximal urethra of incontinent nude rats. Abdominal leak-point pressure and retrograde urethral perfusion pressure were measured both pre- and post-operatively. Smooth muscle cells seeded on the carrier matrix demonstrated long-term improvement, providing immediate bulking effects localized to the urethra.
EARLY PHASE I/II CLINICAL TRIAL RESULTS FOR HUMAN CORD BLOOD STEM CELL INJECTION THERAPY FOR STRESS URINARY INCONTINENCE
Human umbilical cord blood has received increased attention in recent years as a viable source for pluripotent stem cells that can be used in a wide array of applications. In this study, researchers from institutions in Los Angeles, CA, Stony Brook, NY and Seoul, Korea explored whether cord blood stem cells can be used effectively in treating urinary incontinence in women.
32 women with stress urinary incontinence underwent periurethral injection of cord blood stem cells. Patients were evaluated using Incontinence Impact and Incontinence Quality of Life questionnaires. Patients were follwed for an average of 5.1 months and a 50 percent or greater quality of life improvement was noted in 80 percent of the patents after one month, and in 83 percent of patients after three months – suggesting that endoscopic injection of cord blood may be a well-tolerated and safe option for women with stress urinary incontinence.
Source: American Urological Association