Therapeutic effect of human umbilical cord blood progenitor (CD34+) cells in experimentally induced renal failure in adult albino rats. A histological and immunohistochemical study

Abstract

Background Acute renal failure (ARF) is a common clinical problem with grave prognosis and limited therapeutic modalities. Current therapeutic options for ARF are limited to supportive procedures and preventive care, none of which have been definitively shown to alter mortality. Objective The purpose of this study was to assess the therapeutic effect of human umbilical cord blood progenitor CD34+ cells in experimentally induced renal failure in adult albino rats. Methods Twenty-eight adult female albino rats were included in this study. The animals were divided equally into four groups: group I (the control group): Animals of this group received a single intramuscular injection of 10 ml/kg per body weight of normal saline. group II (the ARF group): Animals received a single intramuscular injection of 10ml/kg per body weight of glycerol and saline solution 1:1 (v/v). group III (the PBS-treated group): Animals of this group received intravenous injection of 0.1ml of PBS 24h after inducing ARF. group IV (the CD34+-treated group): Animals of this group received intravenous injection of 0.1ml of PBS containing 2 × 105 CD34+ cells (obtained from the human umbilical cord blood of male babies) per rat 24h after inducing ARF with glycerol. Animals were sacrificed 28 days after the end of the experiment, and their right and left kidneys were excised. The specimens were subjected to different histological techniques and immunohistochemical staining for detecting expression of proliferating cell nuclear antigen (PCNA) in the nuclei of renal tubules. Real-time PCR was carried out to demonstrate the presence of Sry gene (on Y chromosome). For statistical analysis, slides were examined to assess the frequency distribution of different histopathological changes and PCNA index. Optical density of PAS-positive material was also ascertained. Results The renal cortex of group II (ARF group) revealed cellular degenerative changes in the form of cytoplasmic vacuolation and cellular necrotic changes in the form of pyknotic, karyorrhectic, and karyolitic nuclei of renal cortical tubules. At the same time, tubular cell loss was marked in most animals of this group, in addition to the presence of intratubular casts. Loss of brush borders of the proximal convoluted tubules was also observed. Immunohistochemical study of this group revealed very few positive immunoreactive cases for PCNA in tubular cells. Y chromosome-containing cells from male donors were not present in any animal of this group. Group IV (the CD34+-treated group) displayed normal appearance of the renal cortical tubules. Positive immunoreaction for PCNA was observed in many tubular cells compared with other study groups. At the same time, Y chromosome-containing cells from male donors were present in all animals of this group. Conclusion It could be concluded that treatment with CD34+ cells improved most of the histological changes produced by the experimentally induced ARF. Therefore, clinical trials are recommended to evaluate its efficiency in patients with ARF.