Local tissue response to a C-X-C motif chemokine ligand 12 therapy for fecal incontinence in a rabbit model.

This study aimed to determine if local injection of CXCL12 reduces sphincter fibrosis, restores sphincter muscle content, vascularization, and innervation, and recruits progenitor cells in a rabbit model of anal sphincter injury and incontinence. Adult female rabbits were assigned to 3 groups: uninjured/no treatment (control), injured/treated (treated), and injured/no treatment (untreated) (n=4 each). Injured groups were anesthetized and a section of external anal sphincter was removed at the 9:00 o'clock position.

Effects of Age and Multiple Vaginal Births on Lower Urinary Tract Structure and Function in Nonhuman Primates.

Purpose: The relative roles of urinary sphincter damage, aging, and childbirth in stress urinary incontinence (SUI), have not been established. This study was performed to elucidate the roles of these factors.

Methods: The study included: (1) 8 female cynomolgus monkeys (17-19 years of age and 7-8 vaginal births each); (2) six 5-yearold nulliparous monkeys with surgically created chronic urinary sphincter dysfunction; and (3) six 5-year-old, nulliparous, nosurgery controls.

Autologous bone marrow-derived MSCs engineered to express oFVIII-FLAG engraft in adult sheep and produce an effective increase in plasma FVIII levels.

Introduction: Hemophilia A (HA) is the most common X-linked bleeding disorder, occurring in 1 in 5,000 live male births and affecting >1 million individuals worldwide. Although advances in protein-based HA therapeutics have improved health outcomes, current standard-of-care requires infusion 2-3 times per week for life, and 30% of patients develop inhibitors, significantly increasing morbidity and mortality. There are thus unmet medical needs requiring novel approaches to treat HA.

Chemokine Therapy in Cats With Experimental Renal Fibrosis and in a Kidney Disease Pilot Study.

Chronic tubulointerstitial fibrosis is a common final pathway leading to end stage kidney disease in cats and has no effective treatment. The use of cell-based molecules to treat kidney fibrosis may be a promising approach. The objectives were to test the effects of intra-renal chemokine CXCL12 injection in a pre-clinical cat model of unilateral ischemia/reperfusion (I/R)-induced kidney fibrosis and then, within a clinical pilot study, test the safety/feasibility of CXCL12 injection in cats that might have early chronic kidney disease (CKD).

Cell Versus Chemokine Therapy Effects on Cell Mobilization to Chronically Dysfunctional Urinary Sphincters of Nonhuman Primates.

Purpose: A major question remaining in approaches to tissue engineering and organ replacement is the role of native mobilized native cells in the regeneration process of damaged tissues and organs. The goal of this study was to compare the cell mobilizing effects of the chemokine CXCL12 and cell therapy on the urinary sphincter of nonhuman primates (NHP) with chronic intrinsic urinary sphincter dysfunction.

Methods: Either autologous lenti-M-cherry labeled skeletal muscle precursor cells (skMPCs) or CXCL12 were injected directly into the sphincter complex of female NHPs with or without surgery-induced chronic urinary sphincter dysfunction (n=4/treatment condition).

Nonhuman primate model of persistent erectile and urinary dysfunction following radical prostatectomy: Feasibility of minimally invasive therapy.

Objective: Persistent urinary incontinence (UI) and/or erectile dysfunction (ED) occur in 30-50% of post-radical prostatectomy patients regardless of nerve sparing approaches. Identification of potential treatment options for these patients will require testing in an animal model that develops these chronic conditions. The objective was to characterize a nonhuman primate (NHP) model of persistent post-prostatectomy ED and UI and then test the feasibility of periurethral injection of the chemokine CXCL-12.

Efficacy and Initial Safety Profile of CXCL12 Treatment in a Rodent Model of Urinary Sphincter Deficiency.

Disappointing results of skeletal muscle precursor cell (skMPC) therapy for women with intrinsic urinary sphincter deficiency (ISD) associated urinary incontinence has increased interest in alternative sphincter regenerative approaches. This study was to measure the safety and efficacy of the cell homing chemokine CXCL12 versus skMPCs in a rat model of ISD. Thirty-six adult female Sprague Dawley rats were divided into 6 treatment (Tx) conditions: (a) no ISD/noTx [Control]; (b) ISD/noTx; (c) ISD + skMPCs; (d) ISD + 3.

Determinates of muscle precursor cell therapy efficacy in a nonhuman primate model of intrinsic urinary sphincter deficiency.

Background: Cell therapy for intrinsic urinary sphincter deficiency (ISD) in women has been moderately effective, and improvements are needed. To improve treatment efficacy, it is important to better understand determinates of cell efficacy in the different patient cohorts. We have reported that in nonhuman primates the chronicity of ISD may affect cell efficacy, but additional factors (age, psychosocial stress, hormone status, body weight) can be associated with many disease/treatment outcomes in women - and these factors are the focus of this study.

Cell versus Chemokine Therapy in a Nonhuman Primate Model of Chronic Intrinsic Urinary Sphincter Deficiency.

Purpose: Mixed efficacy results of autologous skeletal muscle precursor cell therapy in women with chronic intrinsic urinary sphincter deficiency have increased interest in the therapeutic value of alternative regenerative medicine approaches. The goal of this study was to compare the effects of the cell homing chemokine CXCL12 (C-X-C motif chemokine 12) and skeletal muscle precursor cells on chronic urinary sphincter regeneration in chronic intrinsic urinary sphincter deficiency.

Materials And Methods: Five million autologous skeletal muscle precursor cells or 100 ng CXCL12 were injected in the urinary sphincter complex of adult female cynomolgus monkeys with chronic (6-month history) intrinsic urinary sphincter deficiency.

Local versus intravenous injections of skeletal muscle precursor cells in nonhuman primates with acute or chronic intrinsic urinary sphincter deficiency.

Background: Many factors may influence the efficacy of cell therapy for intrinsic urinary sphincter deficiency (ISD), including the route of administration of the cells and the condition of the sphincter. The goal of this study was to compare local versus intravenous administration of autologous skeletal muscle precursor cells (skMPCs) when administered to nonhuman primates (NHPs) with either acute or chronic ISD.

Methods: Thirty-two adult female monkeys were divided into eight groups (n = 4/group): (1) control; (2) surgically induced ISD/no treatment; (3) acute ISD (6-week duration)/local vehicle only; (4) acute ISD/local skMPC injection; (5) acute ISD/systemic skMPC; (6) chronic ISD (6-month duration)/local vehicle; (7) chronic ISD/local skMPC; (8) chronic ISD/systemic skMPC.