PMID- 30599497 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 2093-4777 (Print) IS - 2093-6931 (Electronic) IS - 2093-4777 (Linking) VI - 22 IP - 4 DP - 2018 Dec TI - Cell Versus Chemokine Therapy Effects on Cell Mobilization to Chronically Dysfunctional Urinary Sphincters of Nonhuman Primates. PG - 260-267 LID - 10.5213/inj.1836126.063 [doi] AB - 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. CONCLUSION: 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. FAU - Williams, J Koudy AU - Williams JK AD - Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA. FAU - Mariya, Silmi AU - Mariya S AD - Primate Research Center Bogor Agricultural University, Bogor, Indonesia. FAU - Suparto, Irma AU - Suparto I AD - Primate Research Center Bogor Agricultural University, Bogor, Indonesia. FAU - Lankford, Shannon S AU - Lankford SS AD - Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA. FAU - Andersson, Karl-Erik AU - Andersson KE AD - Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA. LA - eng GR - R01 DK083688/DK/NIDDK NIH HHS/United States GR - R01 DK 083688/National Institutes of Health/ PT - Journal Article DEP - 20181231 PL - Korea (South) TA - Int Neurourol J JT - International neurourology journal JID - 101534513 PMC - PMC6312977 OTO - NOTNLM OT - Cell mobilization OT - Chemokines OT - Lentivirus transduction OT - Stem cells OT - Urinary sphincter COIS- Conflict of Interest Patent/intellectual property: Dr. Williams has a patent pending as follows: Pub. No.: US 2017/0106050 Al / Pub. Date: Apr. 20, 2017 / "Methods of Treating Incontinence and Other Sphincter Deficiency Disorders." Except for that, no potential conflict of interest relevant to this article was reported. EDAT- 2019/01/03 06:00 MHDA- 2019/01/03 06:01 PMCR- 2018/12/01 CRDT- 2019/01/03 06:00 PHST- 2018/06/07 00:00 [received] PHST- 2018/10/12 00:00 [accepted] PHST- 2019/01/03 06:00 [entrez] PHST- 2019/01/03 06:00 [pubmed] PHST- 2019/01/03 06:01 [medline] PHST- 2018/12/01 00:00 [pmc-release] AID - inj.1836126.063 [pii] AID - inj-1836126-063 [pii] AID - 10.5213/inj.1836126.063 [doi] PST - ppublish SO - Int Neurourol J. 2018 Dec;22(4):260-267. doi: 10.5213/inj.1836126.063. Epub 2018 Dec 31.