Recellularization of Acellular Xeno Kidney Scaffold: An In Vivo Method to Generate Bioartificial Kidney.

Kishor Tardalkar, Nilesh Bhamare, Jeevitaa Kshersagar, Leena Chaudhari, Nimish Deshpande, Jitendra Patil, Rakesh Kumar Sharma, Meghnad G Joshi
Author Information
  1. Kishor Tardalkar: Department of Stem Cells & Regenerative Medicine, D Y Patil Education Society (Deemed to be University), Kolhapur, Maharashtra, India.
  2. Nilesh Bhamare: Department of Stem Cells & Regenerative Medicine, D Y Patil Education Society (Deemed to be University), Kolhapur, Maharashtra, India.
  3. Jeevitaa Kshersagar: Department of Stem Cells & Regenerative Medicine, D Y Patil Education Society (Deemed to be University), Kolhapur, Maharashtra, India.
  4. Leena Chaudhari: Department of Stem Cells & Regenerative Medicine, D Y Patil Education Society (Deemed to be University), Kolhapur, Maharashtra, India.
  5. Nimish Deshpande: Department of Stem Cells & Regenerative Medicine, D Y Patil Education Society (Deemed to be University), Kolhapur, Maharashtra, India.
  6. Jitendra Patil: Department of Radiology, D Y Patil Medical College, D Y Patil Education Society (Deemed to be University), Kolhapur, Maharashtra, India.
  7. Rakesh Kumar Sharma: Department of Obstetrics and Gynaecology, D Y Patil Medical College, D Y Patil Education Society (Deemed to be University), Kolhapur, Maharashtra, India.
  8. Meghnad G Joshi: Department of Stem Cells & Regenerative Medicine, D Y Patil Education Society (Deemed to be University), Kolhapur, Maharashtra, India.

Abstract

A significant hurdle for kidney tissue engineering is reproducing the complex three-dimensional structure of the kidney. In our study, a stepwise approach of generating a reproducible Xeno kidney scaffold from a goat kidney is described, which can be implanted and recellularized by host cells. We have proposed a combination of sodium dodecyl sulfate and Triton-X-100-based protocol to generate a reproducible Xeno kidney scaffold, which was then analyzed by histology, DNA quantification, SEM, and renal angiography. Further, a small portion from the cortico-medullar region of the acellular scaffold was implanted in the rat's kidney subcapsular pocket for a period of 1 month, to check the recruitment of host cells into the scaffold. Post implantation, the extracellular matrix of the scaffold was well preserved and it did not induce any damage or inflammation in the native kidney. Implantation of the Xeno scaffold resulted in apparent early vascularization which helped in the recruitment of the host cells, which was characterized by histology, immunohistochemistry, and scanning electron microscopy. Implanted Xeno scaffold showed AQP-1, Nephrin, α-SMA, and VEGF expression in proximal tubules and renal glomerulus. Importantly, Ki-67 and WTAP-expressing cells were also observed near proximal tubules suggesting a high level of proliferation in the scaffold. Thus, showing the potential of Xeno kidney development that can be recellularized by the host cell to engineer into a functional kidney.

Keywords

References

Basu J, Ludlow JW (2012) Developmental engineering the kidney: leveraging principles of morphogenesis for renal regeneration. Birth Defects Res C Embryo Today 38:30–38 [DOI: 10.1002/bdrc.20224]
Bonandrini B, Figliuzzi M, Papadimou E, Conti S, Benigni A, Remuzzi A, Remuzzi G (2014) Recellularization of well-preserved acellular kidney scaffold using embryonic. Stem Cells 20:1486–1498
Charles River Laboratories (1998) Baseline Haematology and Clinical Chemistry Values for Charles River Wistar Rats (CRL: (WI) BR) as a S.R.P. Avancini et al. /Food and Chemical Toxicology 45 (2007) 2273–2278 2277 Function of Sex and Age. Technical Bulletin, Wilmington. Accessed on November 2006
Cholas R, Salvatore L, Madaghiele M, Sannino A (2017) Sterilization of collagen scaffolds designed for peripheral nerve regeneration: effect on microstructure, degradation and cellular colonization. Mater Sci Eng C71:335–344
Datta P, Ayan B, Ozbolat IT (n.d.) Bioprinting for vascular and vascularized tissue biofabrication. Acta Biomater 51:1–20
Eckardt KU, Kurtz A (2005) Regulation of erythropoietin production. Eur J Clin Investig 35:13–19 [DOI: 10.1111/j.1365-2362.2005.01525.x]
Giraldo-gomez DM, Leon-mancilla B, Del P-a ML, Sotres-vega A, Villalba-caloca J (2016) Trypsin as enhancement in cyclical tracheal decellularization: morphological and biophysical characterization mater. Sci Eng C59:930–937
Gupta P, Mandal BB (2021) Tissue-engineered vascular grafts: emerging trends and technologies. Adv Funct Mater 31(33):2100027 [DOI: 10.1002/adfm.202100027]
Jha V, Garcia-garcia G, Iseki K, Li Z, Naicker S, Plattner B, Saran R, Wang AY, Yang C (2013) Global kidney disease 3 chronic kidney disease: global dimension and perspectives. Lancet 382:260–272 [DOI: 10.1016/S0140-6736(13)60687-X]
Khan RL, Khraibi AA, Dumée LF, Corridon PR (2023) From waste to wealth: repurposing slaughterhouse waste for xenotransplantation. Front Bioeng Biotechnol 11:1091554
Liyanage T, Ninomiya T, Jha V, Neal B, Patrice HM, Okpechi I, Zhao M, Lv J (2013) Worldwide access to treatment for end-stage kidney disease. Lancet 385:1975–1982 [DOI: 10.1016/S0140-6736(14)61601-9]
Martin CE, Jones N (2018) Nephrin signaling in the podocyte: an updated view of signal regulation at the slit diaphragm and beyond. Front Endocrinol 9:1–12 [DOI: 10.3389/fendo.2018.00302]
Naghavi M, Abajobir AA, Abbafati C, Abbas KM, Abd-Allah F, Abera SF, Aboyans V et al (2017) Global, regional, and national age-sex specifc mortality for 264 causes of death, 1980–2016: a systematic analysis for the global burden of disease study 2016. Lancet 390:1151–1210 [DOI: 10.1016/S0140-6736(17)32152-9]
Pedersen TO, Blois AL, Xing Z, Xue Y, Sun Y, Finne-wistrand A, Akslen LA, Lorens JB, Leknes KN, Fristad I, Mustafa K (2013) Endothelial microvascular networks affect gene-expression profiles and osteogenic potential of tissue-engineered constructs. Stem Cell Res Ther 4:52 [DOI: 10.1186/scrt202]
Rogers SA, Miller SB, Hammerman MR, Miller B (2019) Altered EGF expression and thyroxine metabolism in kidneys following acute ischemic injury in rat. Am J Physiol Renal Physiol 270:21–30 [DOI: 10.1152/ajprenal.1996.270.1.F21]
Tardalkar K, Desai S, Adnaik A, Bohara R, Joshi M (2017) Novel approach toward the generation of tissue engineered heart valve by using combination of antioxidant and detergent: a potential therapy in cardiovascular tissue engineering. Tissue Eng Regen Med 14:755–762 [DOI: 10.1007/s13770-017-0070-1]
Thurner LR, Höcherl K (2019) Role of protease-activated receptor 2 in regulation of renin synthesis and secretion in mice. Naunyn Schmiedeberg’s Arch Pharmacol 392:1401 [DOI: 10.1007/s00210-019-01677-4]
Tokuda S (2019) Regulation of epithelial cell functions by the osmolality and hydrostatic pressure gradients: a possible role of the tight junction as a sensor. Int J Mol Sci 20:3513 [DOI: 10.3390/ijms20143513]
Wragg NM, Burke L, Wilson SL (2019) A critical review of current progress in 3D kidney biomanufacturing: advances, challenges, and recommendations. Ren Replac Ther 7:1–16
Zada MH, Kumar A, Elmalak O, Mechrez G, Domb AJ, Lezion R (2019) Effect of ethylene oxide and gamma (γ-) sterilization on the properties of a PLCL polymer material in balloon implants ACS omega. ACS Omega 4:21319–21326 [DOI: 10.1021/acsomega.9b02889]
Zambon JP, Magalhaes RS, Ko I, Ross CL, Orlando G, Peloso A, Atala A, Yoo JJ, Zambon JP, Magalhaes RS, Ko I, Ross L, Orlando G, Peloso A, Atala A (2014) Kidney regeneration: where we are and future perspectives. World J Nephrol 3:24–30 [DOI: 10.5527/wjn.v3.i3.24]
Zehnder D, Bland R, Williams MC, Ninch RWMC, Howie AJ, Stewart PM, Hewison M (2001) Extrarenal expression of 25-hydroxyvitamin D3-1α-hydroxylase. J Clin Endocrinol Metabol 86:888–894
Zhou M, Wang H, Zhu J, Chen W, Wang L, Liu S, Li Y, Wang L, Liu Y, Yin P, Liu J (2016) Cause-specific mortality for 240 causes in China during 1990–2013: a systematic subnational analysis for the Global Burden of Disease Study 2013. Lancet 387:251–272
Zöllner FG, Zimmer F, Klotz S, Hoeger S, Schad LR, Bildgebung F, Untersuchung T (2014) Functional imaging of acute kidney injury at 3 Tesla: investigating multiple parameters using DCE-MRI and a two-compartment filtration model. Z Med Phys 25:58–65

MeSH Term

Rats
Animals
Tissue Scaffolds
Tissue Engineering
Extracellular Matrix
Kidney
DNA

Chemicals

DNA

Word Cloud

Similar Articles

Cited By