Int Neurourol J.  2018 Dec;22(4):260-267. 10.5213/inj.1836126.063.

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

• Williams J
• Mariya S
• Suparto I
• Lankford S
• Andersson

• KMID: 2431867
• DOI: http://doi.org/10.5213/inj.1836126.063

Abstract

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). All monkeys had partial bone marrow transplantation with autologous lenti-green fluorescent protein (GFP) bone marrow cells prior to treatment. Labeled cells were identified, characterized and quantified using computer-assisted immunohistochemistry 6 months posttreatment.
RESULTS
GFP-labeled bone marrow cells (BMCs) were identified in the bone marrow and both BMCs and skMPCs were found in the urinary sphincter at 6-month postinjection. BMCs and skMPCs were present in the striated muscle, smooth muscle, and lamina propria/urothelium of the sphincter tissue. Sphincter injury increased the sphincter content of BMCs when analyzed 6-month postinjection. CXCL12 treatment, but not skMPCs, increased the number of BMCs in all layers of the sphincter complex (P < 0.05). CXCL12 only modestly (P=0.15) increased the number of skMPCs in the sphincter complex.
CONCLUSIONS
This dual labeling methodology now provides us with the tools to measure the relative number of locally injected cells versus bone marrow transplanted cells. The results of this study suggest that CXCL12 promotes mobilization of cells to the sphincter, which may contribute more to sphincter regeneration than injected cells.

Keyword

Lentivirus transduction; Urinary sphincter; Cell mobilization; Stem cells; Chemokines

MeSH Terms

Bone Marrow
Bone Marrow Cells
Bone Marrow Transplantation
Cell- and Tissue-Based Therapy
Chemokine CXCL12
Chemokines
Female
Haplorhini
Humans
Immunohistochemistry
Muscle, Skeletal
Muscle, Smooth
Muscle, Striated
Primates*
Regeneration
Stem Cells
Tissue Engineering
Chemokine CXCL12
Chemokines