Ronald Jankowski

1-year follow-up of autologous muscle-derived stem cell injection pilot study to treat stress urinary incontinence

We hereby report a 1-year follow-up on eight women in the first North America trial in which stress urinary incontinence (SUI) was treated with muscle-derived stem cell injections. Mean and median follow-up in this group was 16.5 and 17xa0months (range 3–24xa0months). Improvement in SUI was seen in five of eight women, with one achieving total continence. Onset of improvement was between 3 and 8xa0months after injection. Cure or improvement continued at a median of 10xa0months. No serious adverse events were reported.

Modeling Stem Cell Population Growth: Incorporating Terms for Proliferative Heterogeneity

Expansion of the undifferentiated stem cell phenotype is one of the most challenging aspects in stem cell research. Clinical protocols for stem cell therapeutics will require standardization of defined culture conditions. A first step in the development of predictable and reproducible, scalable bioreactor processes is the development of mathematical growth models. This paper provides practical models for describing cell growth in general, which are particularly well suited for examining stem cell populations. The nonexponential kinetics of stem cells derive from proliferative heterogeneity, which is biologically recognized as mitosis, quiescence, senescence, differentiation, or death. Here, we examined the assumptions of the Sherley model, which describes heterogeneous expansion in the absence of cell loss. We next incorporated terms into the model to account for A) cell loss or apoptosis and B) cell differentiation. We conclude that the basic assumptions of the model are valid and a high correlation between the modified equations and experimental data obtained using muscle‐derived stem cells was observed. Finally, we demonstrate an improved estimation of the kinetic parameters. This study contributes to both the biological and mathematical understanding of stem cell dynamics. Further, it is expected that the models will prove useful in establishing standardization of cell culture conditions and scalable systems and will be required to develop clinical protocols for stem cell therapeutics.

Effect of retroviral transduction on human endothelial cell phenotype and adhesion to Dacron vascular grafts

PURPOSEnRetroviral transduction for genetic enhancement of endothelial cell (EC) anti-thrombotic phenotype offers potential for improving the clinical success of vascular graft seeding; however, application of this technique may bring concomitant alteration in cell functionality.nnnMETHODSnHuman microvascular ECs were transduced with a retroviral vector encoding for the marker gene beta-galactosidase. Transduced endothelial cells (rtECs) and nontransduced endothelial cells (ntECs) were evaluated by flow cytometry for expression of intercellular adhesion molecule (ICAM)-1 and tissue factor (TF) on both smooth (coverslips) and graft (Dacron, 6 mm inside diameter) surfaces under static and shear exposed conditions. Graft EC retention was measured after 6-hour pulsatile perfusions. Platelet and neutrophil adherence was measured on perfused coverslips.nnnRESULTSnLower levels of ICAM-1 were expressed by rtECs on coverslips under both static (p < 0.01 vs static ntECs) and shear exposed conditions (p < 0.01 vs static and shear ntECs). Accordingly, fewer polymorphonuclear leukocytes adhered to rtEC monolayers (p < 0.01 vs ntECs). No difference in ICAM-1 and TF expression by static graft seeded rtECs and ntECs was observed. However, graft-seeded rtECs that were exposed to wall shear stress displayed less TF than sheared ntECs (p < 0.05). Transduction did not affect EC retention to the sheared graft surface.nnnCONCLUSIONSnThese data suggest that retroviral transduction does not elicit a prothrombotic/proinflammatory phenotype, rather indices of these states appear in some conditions to be reduced. Further, transduction does not adversely affect EC adherence to Dacron graft surfaces under arterial hemodynamics.

New technology assessment and current and upcoming therapies for underactive bladder

Stakeholders from around the world came together to address the unmet needs of underactive bladder (UAB) at the 3rd International Congress for Underactive Bladder.

Muscle‐derived Stem Cell Therapy for Stress Urinary Incontinence

The aim of the present article is to overview the potential of muscle‐derived stem cells and other cellular therapy for urethral regeneration and to review the clinical experiences of its application in patients with stress urinary incontinence.

Effects of Diabetes Mellitus on the Biomechanical Properties of the Female Rat Urethra in the Passive State

Patients with diabetes mellitus (DM) suffer impaired lower urinary tract dysfunctions. The purpose of the current study was to evaluate the effects of DM on the passive biomechanical properties of the female rat urethra. DM was induced by injection of streptozotocin. Urethras were excised and mounted in an ex-vivo testing system. EDTA was added to the bath to inactivate smooth muscle. Continuous outer diameter measurements were made at proximal, middle, and distal portions of the urethra with a laser micrometer during stepwise increases of static, intraurethral pressure (0 to 20 mmHg). Compliance and beta stiffness were calculated from measured data. Healthy urethras served as controls. Statistical comparisons were made via ANOVA. The control tissue was most compliant proximally and decreased significantly along the length. This compliance gradient vanished with DM. A significant decrease in compliance and increase in beta stiffness was noted for 10 wk DM compared to controls. These findings suggest that DM has a large effect on the biomechanical properties of the urethra.Copyright

Effects of diabetes mellitus on the biomechanical properties of the female rat urethra

The effects of diabetes mellitus (DM) on bladder function are well described, but little is known of effects on the outlet function of the urethra. In the present study, biomechanical properties of urethras from DM and healthy female rats were compared. At 3, 5, and 10 weeks following streptozotocin induction of DM, urethras were excised from anesthetized rats maintaining in vivo length, mounted onto tees at in vivo length in an established ex vivo vascular testing system, and maintained in an oxygenated circulating bath of physiological media at 37/spl deg/C. Stepwise intraurethral pressure increments from 0-20 mmHg were applied and diameters were simultaneously recorded at proximal, mid, and distal positions. Urethras from age-matched rats served as controls. There was a proximal-distal decreasing gradient in compliance in normal urethras, and a progressive increase in beta stiffness from 3-10 weeks following DM in the mid and proximal regions to values indistinguishable from the distal. Increasing urethral stiffness in DM results in a collapse of the compliance gradient leading to increased outlet resistance for a bladder in which contractility is already compromised. Thus, DM effects on the urethra interact with those on the bladder to further compromise lower urinary tract function.

Establishing a system for the study of urethral biomechanical function

By applying experimental concepts and principles originally established in the study of blood vessel biomechanics, we are exploring various aspects of lower urinary tract function, dysfunction, and treatment effects on tissue properties and performance. We demonstrate here the feasibility of using a modified ex vivo vascular perfusion apparatus for urethral functional studies. Through administration of various pharmacologic agents, and against applied luminal pressures, we demonstrate control over urethral smooth and striated muscle contractile elements. The ability to measure such physiologic responses provides the basis for performing novel functional studies pertaining to the role of each component in overall urethral function and biomechanics. Therefore, the use of this system to evaluate ex vivo physiology and biomechanical properties will advance the understanding of underlying principles of both normal and abnormal urethral function.