Potential Use of Autologous Renal Cells from Diseased Kidneys for the Treatment of Renal Failure.

Sunil K George,John D Jackson,Tamer Aboushwareb,James J Yoo,Mehran Abolbashari,Anthony Atala,Shree Ram Singh

doi:10.1371/journal.pone.0164997

Sunil K George, John D Jackson + Show 5 more

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https://doi.org/10.1371/journal.pone.0164997

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Abstract

Chronic kidney disease (CKD) occurs when certain conditions cause the kidneys to gradually lose function. For patients with CKD, renal transplantation is the only treatment option that restores kidney function. In this study, we evaluated primary renal cells obtained from diseased kidneys to determine whether their normal phenotypic and functional characteristics are retained, and could be used for cell therapy. Primary renal cells isolated from both normal kidneys (NK) and diseased kidneys (CKD) showed similar phenotypic characteristics and growth kinetics. The expression levels of renal tubular cell markers, Aquaporin-1 and E-Cadherin, and podocyte-specific markers, WT-1 and Nephrin, were similar in both NK and CKD kidney derived cells. Using fluorescence- activated cell sorting (FACS), specific renal cell populations were identified and included proximal tubular cells (83.1% from NK and 80.3% from CKD kidneys); distal tubular cells (11.03% from NK and 10.9% from CKD kidneys); and podocytes (1.91% from NK and 1.78% from CKD kidneys). Ultra-structural analysis using scanning electron microscopy (SEM) revealed microvilli on the apical surface of cultured cells from NK and CKD samples. Moreover, transmission electron microscopy (TEM) analysis showed a similar organization of tight junctions, desmosomes, and other intracellular structures. The Na+ uptake characteristics of NK and CKD derived renal cells were also similar (24.4 mmol/L and 25 mmol/L, respectively) and no significant differences were observed in the protein uptake and transport characteristics of these two cell isolates. These results show that primary renal cells derived from diseased kidneys such as CKD have similar structural and functional characteristics to their counterparts from a normal healthy kidney (NK) when grown in vitro. This study suggests that cells derived from diseased kidney may be used as an autologous cell source for renal cell therapy, particularly in patients with CKD or end-stage renal disease (ESRD).

Highlights

Chronic kidney disease (CKD) is a global health problem, which can lead to end-stage renal failure and eventually death if not treated [1, 2]
Periodic acid-Schiff (PAS) staining (Fig 1B) and Masson’s Trichrome (MT) staining (Fig 1C) of normal kidneys (NK) sections revealed a fine interstitium in the renal cortex and a thin basement membrane in the glomerulus
Several initial cell-therapy studies using renal cells isolated from normal kidney (NK) showed functional improvement

Summary

Introduction

Chronic kidney disease (CKD) is a global health problem, which can lead to end-stage renal failure and eventually death if not treated [1, 2]. Dialysis replicates the renal filtering process by removing toxic substances from the blood. This can result in anemia, low blood pressure, increased potential for infection and failure to restore other necessary renal functions, such as erythropoietin production and activation of vitamin D [7]. It contributes to the overall inefficient recovery of renal function and morbidity All these point to an urgent need to develop alternative strategies for the treatment of CKD

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