WP 2

Repairing delivery induced anal sphincter insufficiency

With this project we aim for developing novel tools for reconstructing the muscle defects, seen in the anal sphincter due to injuries during delivery, leading to anal incontinence. We will combine stem cells with different types of scaffolds and inject them in the defect of the anal sphincter, with the prime purpose of developing functional muscle tissue, there are able to improve the tonus of the anal sphincter, and thereby ameliorate the incontinence

Background

Annually about 400 patients with anal incontinence are seen at Odense University Hospital at the department of gynecology and obstetrics and the department of general surgery. The most frequent cause is a rupture of the internal and external sphincter during delivery The incidence of severe sphincter rupture caused by giving birth in Region Syddanmark in 2012 was 62 out of 100.000 = 0,062%

The treatment of anal incontinence depends on the severity of the condition. First-line treatment is dietary regulations with focus on lots of fibers, different regimes of stool regulatory medicament’s and physiotherapy with biofeedback. If the anal incontinence occurs within the first three weeks after delivery, the woman will be offered secondary suturing.

A group of women will after conservative treatment still have symptoms of anal incontinence. Some of these women are offered surgery. The most commonly used surgical technique is removal of the fibrous tissue between the ends of the ruptured sphincter, the ends are then connected with an overlaps suture. Only 6-79% of the patients will gain anal continence 20-120 month after surgery. The result of surgery is disappointing, and is leaving a group of more severely affected women, which are not cured of their symptoms. In these cases interventions with reparation on the sphincter using autologous  muscle stem cell transplantation could be considered.

Approach

We hypothesize that myoblast when embedded in hydrogels will enter a quiescent phase, and when the hydrogel embedded myoblast are implanted in vivo, the hydrogel will be degraded, and the cells will be released in a synchronously activated state, a situation optimal for regeneration.

The myogenic stem cell will when injected in an anal sphincter with visible lesions detected by ultrasound regenerate the sphincter muscle and reestablish  tonus.


Research Interest

Our interests are regeneration of skeletal and smooth muscle with the focus on the application in restoration of damaged muscle. This includes research on several levels: basic biology of muscle regeneration, test of scaffold for 3D support of muscle formation, evaluation in animal models, and clinical trials.  In studies on basic biology we look at mechanisms that activate quiescent stem cells, keep them proliferating and induce differentiation.3D scaffolds are tested in vitro and in vivo in animal models, and we develop scaffolds for delivery of cells and biological active compounds.

The muscle group at Department of Pathology is partner in SDU Muscle Research Cluster, SMRC http://www.sdu.dk/Om_SDU/Institutter_centre/SMRC


Figur 2

Research group

Henrik Daa Schrøder

Group leader
CV  |  Publications


+45 6541 4801
Henrik.daa.schroeder@rsyd.dk

Research interest

Our interests are regeneration of skeletal and smooth muscle with the focus on the application in restoration of damaged muscle. This includes research on several levels: basic biology of muscle regeneration, test of scaffold for 3D support of muscle formation, evaluation in animal models, and clinical trials. In studies on basic biology we look at mechanisms that activate quiescent stem cells, keep them proliferating and induce differentiation.3D scaffolds are tested in vitro and in vivo in animal models, and we develop scaffolds for delivery of cells and biological active compounds.
The muscle group at Department of Pathology is partner in SDU Muscle Research Cluster, SMRC http://www.sdu.dk/Om_SDU/Institutter_centre/SMRC

Lab page »

Selected publications

  1. Petersson SJ, Jorgensen LH, Andersen DC, Norgaard RC, Jensen CH, Schroder HD: SPARC is up-regulated during skeletal muscle regeneration and inhibits myoblast differentiation. Histology and Histopathology 2013, 28:1451-60.
  2. Sellathurai J, Cheedipudi S, Dhawan J, Schroder HD: A Novel In Vitro Model for Studying Quiescence and Activation of Primary Isolated Human Myoblasts. Plos One 2013, 8.
  3. Jorgensen LH, Sellathurai J, Davis EE, Thedchanamoorthy T, Al-Bader RWA, Jensen CH, Schroder HD: Like 1 Homolog (Dlk1): A Marker for Rhabdomyosarcomas Implicated in Skeletal Muscle Regeneration. Plos One 2013, 8
  4. Andersen DC, Kristiansen GQ, Jensen L, Fuchtbauer E-M, Schroder HD, Jensen CH: Quantitative gene expression profiling of CD45(+) and CD45(-) skeletal muscle-derived side population cells. Cytometry Part A 2012, 81A:72-80.
  5. Burns JS, Rasmussen PL, Larsen KH, Schroder HD, Kassem M: Parameters in Three-Dimensional Osteospheroids of Telomerized Human Mesenchymal (Stromal) Stem Cells Grown on Osteoconductive Scaffolds That Predict In Vivo Bone-Forming Potential. Tissue Engineering Part A 2010, 16:2331-42
  6. Mahmood A, Harkness L, Schroder HD, Abdallah BM, Kassem M: Enhanced Differentiation of Human Embryonic Stem Cells to Mesenchymal Progenitors by Inhibition of TGF-beta/Activin/Nodal Signaling Using SB-431542. Journal of Bone and Mineral Research 2010, 25:1216-33.
  7. Pacheco-Pinedo EC, Budak MT, Zeiger U, Jorgensen LH, Bogdanovich S, Schroder HD, Rubinstein NA, Khurana TS: Transcriptional and functional differences in stem cell populations isolated from extraocular and limb muscles. Physiological Genomics 2009, 37:35-42.
  8. Prokhorova TA, Harkness LM, Frandsen U, Ditzel N, Schroder HD, Burns JS, Kassem M: Teratoma Formation by Human Embryonic Stem Cells Is Site Dependent and Enhanced by the Presence of Matrigel. Stem Cells and Development 2009, 18:47-54. Andersen DC, Schroder HD, Jensen CH: Non-cultured adipose-derived CD45(-) side population cells are enriched for progenitors that give rise to myofibres in vivo. Experimental Cell Research 2008, 314:2951-64.

Funding