TY - JOUR
T1 - Contribution of bone marrow-derived cells to in situ engineered tissue capsules in a rat model of chronic kidney disease
AU - Bezhaeva, Taisiya
AU - Geelhoed, Wouter J.
AU - Wang, Dong
AU - Yuan, Haoyong
AU - van der Veer, Eric P.
AU - van Alem, Carla M. A.
AU - Damanik, Febriyani F. R.
AU - Qiu, Xuefeng
AU - van Zonneveld, Anton-Jan
AU - Moroni, Lorenzo
AU - Li, Song
AU - Rotmans, Joris I.
N1 - Funding Information:
This study was supported by a VIDI grant ( 016.156.328 ) awarded to J.I. Rotmans and funding from the National Institute of Health ( EB012240 and HL083900 ) awarded to S. Li. We would like to thank Reshma A. Lalai for her excellent assistance in performing experiments and data analysis. Dr. Kei S. Iwamoto, from UCLA Radiation Oncology department for his excellent assistance in bone marrow transplantation experiments.
Funding Information:
Flow cytometry was performed in the UCLA Jonsson Comprehensive Cancer Center (JCCC) and Center for AIDS Research Flow Cytometry Core Facility that is supported by National Institutes of Health awards P30 CA016042 and 5P30 AI028697, and by the JCCC JCCC , the UCLA AIDS Institute , the David Geffen School of Medicine at UCLA, the UCLA Chancellor's Office , and the UCLA Vice Chancellor's Office of Research .
Funding Information:
This study was supported by a VIDI grant (016.156.328) awarded to J.I. Rotmans and funding from the National Institute of Health (EB012240 and HL083900) awarded to S. Li. We would like to thank Reshma A. Lalai for her excellent assistance in performing experiments and data analysis. Dr. Kei S. Iwamoto, from UCLA Radiation Oncology department for his excellent assistance in bone marrow transplantation experiments.Flow cytometry was performed in the UCLA Jonsson Comprehensive Cancer Center (JCCC) and Center for AIDS Research Flow Cytometry Core Facility that is supported by National Institutes of Health awards P30 CA016042 and 5P30 AI028697, and by the JCCCJCCC, the UCLA AIDS Institute, the David Geffen School of Medicine at UCLA, the UCLA Chancellor's Office, and the UCLA Vice Chancellor's Office of Research.
Publisher Copyright:
© 2018
PY - 2019/2
Y1 - 2019/2
N2 - Tissue engineered blood vessels (TEBVs) hold great promise for clinical use in patients with end stage renal disease (ESRD) requiring vascular access for hemodialysis. A promising way to make TEBVs is to exploit foreign body response (FBR) of polymeric rods used as templates. However, since the FBR predominantly involves bone marrow (BM) derived cells and ESRD coincides with impaired function of BM, it is important to assess the generation of TEBVs in conditions of renal failure. To this end, we implanted polymer rods in the subcutis of rats after BM-transplantation with OFF-labeled BM cells in a model of chronic kidney disease (CKD). At 3 weeks after implantation, rods were encapsulated by tissue capsule (TC) composed of collagen, myofibroblasts and macrophages. On average, 13% of CD68(+) macrophages were GFP(+), indicating BM origin. Macrophage-to-myofibroblasts differentiation appeared to play an important role in TC formation as 26% of SMA(+)/GFP(+) myofibroblasts co-expressed the macrophage marker CD68. Three weeks after rod implantation, the cellular response changed towards tissue repair, characterized by 40% increase in CD68(+)/CD163(+) repair associated macrophages and 95% increase in TGF beta and IL10 gene expression as compared to TCs harvested at 1 week. These results show that both BM derived and tissue resident cells, contribute to TC formation, whereas macrophages serve as precursors of myofibroblasts in mature TCs. Finally, the presence of CKD did not significantly alter the process of TC formation, which holds the potential to support our approach for future clinical use in ESRD patients.
AB - Tissue engineered blood vessels (TEBVs) hold great promise for clinical use in patients with end stage renal disease (ESRD) requiring vascular access for hemodialysis. A promising way to make TEBVs is to exploit foreign body response (FBR) of polymeric rods used as templates. However, since the FBR predominantly involves bone marrow (BM) derived cells and ESRD coincides with impaired function of BM, it is important to assess the generation of TEBVs in conditions of renal failure. To this end, we implanted polymer rods in the subcutis of rats after BM-transplantation with OFF-labeled BM cells in a model of chronic kidney disease (CKD). At 3 weeks after implantation, rods were encapsulated by tissue capsule (TC) composed of collagen, myofibroblasts and macrophages. On average, 13% of CD68(+) macrophages were GFP(+), indicating BM origin. Macrophage-to-myofibroblasts differentiation appeared to play an important role in TC formation as 26% of SMA(+)/GFP(+) myofibroblasts co-expressed the macrophage marker CD68. Three weeks after rod implantation, the cellular response changed towards tissue repair, characterized by 40% increase in CD68(+)/CD163(+) repair associated macrophages and 95% increase in TGF beta and IL10 gene expression as compared to TCs harvested at 1 week. These results show that both BM derived and tissue resident cells, contribute to TC formation, whereas macrophages serve as precursors of myofibroblasts in mature TCs. Finally, the presence of CKD did not significantly alter the process of TC formation, which holds the potential to support our approach for future clinical use in ESRD patients.
KW - In situ vascular tissue engineering
KW - Chronic kidney disease
KW - Hemodialysis vascular access
KW - Bone-marrow lineage tracing
KW - Foreign body response
KW - FOREIGN-BODY RESPONSE
KW - STEM-CELLS
KW - RESIDENT MACROPHAGES
KW - MESENCHYMAL TRANSITION
KW - PROGENITOR CELLS
KW - BLOOD-VESSELS
KW - EXPRESSION
KW - HYPERPLASIA
KW - FIBROSIS
KW - SEGMENTS
U2 - 10.1016/j.biomaterials.2018.12.014
DO - 10.1016/j.biomaterials.2018.12.014
M3 - Article
SN - 0142-9612
VL - 194
SP - 47
EP - 56
JO - Biomaterials
JF - Biomaterials
ER -