Aberrant Differentiation of Human Pluripotent Stem Cell-Derived Kidney Precursor Cells inside Mouse Vascularized Bioreactors
| Autor: | Susan J. Kimber, Brian Derby, Parisa Ranjzad, Jason Wong, Adrian S. Woolf, Jessica Jinks, Amir P Salahi, Ioannis Bantounas |
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| Rok vydání: | 2020 |
| Předmět: |
Pluripotent Stem Cells
Pathology medicine.medical_specialty Cell Culture Techniques 030232 urology & nephrology Mice SCID 030204 cardiovascular system & hematology Kidney Experimental Nephrology and Genetics: Research Article Cell Line Mice 03 medical and health sciences Bioreactors 0302 clinical medicine Vascularity In vivo Precursor cell medicine Animals Humans Induced pluripotent stem cell business.industry Cell Differentiation Histology Renal dysplasia medicine.anatomical_structure Heterografts medicine.symptom business Transforming growth factor |
| Zdroj: | Nephron Clin Pract |
| ISSN: | 2235-3186 1660-8151 |
| DOI: | 10.1159/000509425 |
| Popis: | Background: Numerous studies have documented the in vitro differentiation of human pluripotent stem cells (hPSCs) into kidney cells. Fewer studies have followed the fates of such kidney precursor cells (KPCs) inside animals, a more life-like setting. Here, we tested the hypothesis that implanting hPSC-derived KPCs into an in vivo milieu surgically engineered to be highly vascular would enhance their maturation into kidney tissues. Methods: 3D printed chambers containing KPCs were implanted into the thighs of adult immunodeficient mice. In some chambers, an arterial and venous flow-through (AVFT) was surgically fashioned. After 3 weeks and 3 months, implants were studied by histology, using qualitative and quantitative methods. Results: After 3 weeks, chambers containing AVFTs were richer in small vessels than contralateral chambers without AVFTs. Glomeruli with capillary loops and diverse types of tubules were detected in all chambers. At 3 months, chambers contained only rudimentary tubules and glomeruli that appeared avascular. In chambers with AVFTs, prominent areas of muscle-like cells were also detected near tubules and the abnormal tissues immunostained for transforming growth factor β1. These features have similarities to renal dysplasia, a typical histological signature of human congenital kidney malformations. Conclusions: This study urges a note of caution regarding the in vivo fates of hPSC-derived kidney precursors, with pathological differentiation appearing to follow a period of increased vascularity. |
| Databáze: | OpenAIRE |
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