Stem Cell Therapy: A Future Treatment of Stress Urinary Incontinence

Dmitriy Nikolavasky, M.D.; Klaudia Stangel-Wójcikiewicz, M.D.; Malgorzata Stec, M.D.; Michael B. Chancellor, M.D.

Disclosures

Semin Reprod Med. 2011;29(1):61-70. 

In This Article

Abstract and Introduction

Abstract

The main urinary continence mechanism in human is the striated muscle rhabdosphincter that forms a ring around the mid-urethra. Cellular therapy and the use of stem cells transplanted into the site of the rhabdosphincter in a setting of stress urinary incontinence (SUI) may augment sphincter regeneration. Implanted cells may also release trophic factors promoting muscle and nerve integration into this muscle. We review the use of cellular therapy for SUI and our experience with the development of muscle-derived stem cells.

Introduction

More than 200 million people worldwide suffer from urinary incontinence.[1,2] The most common type is stress urinary incontinence (SUI).[3] Some of the known risks for acquiring SUI are high parity, advanced age, and obesity.[4] Trauma to the pelvic floor musculature, connective tissue, or nerves later in life becomes the most important risk factor for development of SUI.[5–8]

SUI is further categorized as urethral hypermobility, intrinsic sphincter deficiency (ISD), or both.[9] Urethral hypermobility results from weakened bladder neck support, which in turn leads to the lack of transmission of intra-abdominal pressure to the proximal urethra. ISD is distinguished by failure of the urethral closure. These two mechanisms represent extremes of the spectrum of SUI; most patients have varying degrees of both disorders.[10]

Previous attempts to treat SUI with pharmaceuticals including α-agonists have not been highly successful clinically.[11] Temporary success was achieved with minimally invasive treatments with injectable bulking agents including polytetrafluoroethylene,[12] bovine collagen,[13] silicone,[14] carbon beads,[15] and autologous ear chondrocytes.[16] Unfortunately, long-term complications of these procedures included chronic inflammatory reactions, foreign body giant cell responses, periurethral abscesses, erosion of the bladder and urethra, particle migration, bladder outlet obstruction causing urinary retention, and even pulmonary embolism.[17–20]

Currently, the most exciting and promising incontinence research is focused on regenerative repair of damaged rhabdosphincter with stem cell therapy.[21] The use of embryonic stem cells is controversial and is practically limited in part due to ethical concerns, increased potential for tumorigenicity, and governmental regulations.[22] In this setting, isolation and usefulness of autologous adult stem cells would be highly valuable. One example of autologous multipotent stem cells used in cell-based therapies is bone marrow stromal cells. However, harvesting bone marrow stem cells is limited by the complexity and pain of the procedure, and potentially a low number of harvested cells. Fortunately, there are alternative sources of autologous multipotent adult stem cells. These are muscle-derived stem cells (MDSCs) and adipose-derived stem cells (ADSCs), which are easier and less painful to obtain in large quantities.

In the future the treatment of SUI may consist of two routine visits to a urologist or a gynecologist. In the first visit the physician would take a small skeletal muscle biopsy with a small-caliber needle and send it to an approved laboratory for preparation of MDSCs. Several weeks later, in the second visit, the stem cells would be injected into the patient's urethral sphincter under local anesthesia (Fig. 1).

Figure 1.

Autologous stem cell injection therapy for stress urinary incontinence. Autologous stem cells are obtained with a biopsy of tissue, the cells are dissociated and expanded in culture, and the expanded cells are implanted into the same host. Used with permission from John Wiley & Sons, Inc.; Neurourol Urodyn 2007;26(7):967.

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