الفهرس 
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Abstract
Chronic kidney disease (CKD) is a critical issue worldwide with an increasing incidence. Treatments available for CKD include dialysis and renal transplantation which have several drawbacks. Xenogeneic cell therapy provides a promising new option in the field of regenerative medicine by using cells from different tissues of animals as source for treating human diseases. Remarkable pre-clinical research needed for the demonstration of efficacy and safety of utilizing xenogeneic cells as therapeutic drug for the progress of this field. This study was carried out to investigate the possible therapeutic effect of both camel and sheep Wharton’s jelly MSC on canine CKD model. The study comprised two parts. Part I was a pilot study to determine the suitable method to induce surgically CKD model in dogs. Part II carried out to investigate the therapeutic effect of both CWJ-MSCs and SWJ-MSCs on the induced CKD model. Part I, the pilot study was applied in three dogs, each one represents one model. Model I, induced by excision of one pole of right kidney with removal of contralateral kidney after two weeks from first operation. Model II, induced by excision of two poles of right kidney with removal of contralateral kidney after two weeks from the first operation. Model III, was induced by ligation of two renal arterial branches of right kidney, with removal of contralateral kidney after two weeks from the first operation. The results of this study showed that model (2) was considered the best technique for developing a model of canine CKD with persistent uremia.. According to the IRIS staging system in dogs, model (2) represented stage three of CKD with moderate expression of kidney degenerative genes (KIM-1& NGAL) and α-SMA in the interstitial tissue and moderate glomerulointerstitial nephritis. The dog in this model became uremic and remained stable for a long time which would allow experimental manipulation. Part II of the study, was performed on nine dogs divided into three groups. chronic kidney disease model induced in dogs by using 5/6 nephrectomy technique. The collected MSCs were isolated and cultured then identified by morphology and flow cytometric analysis. MSCs were injected intrarenal with ultrasonographic guidance in a dose of (5× 106 cells) in two doses. Serum was collected regularly for kidney function test. Kidney tissue specimens were collected for histopathology and identification of NGAL, KIM-1, and EGFR genes by real time PCR. Serum urea and creatinine levels were significantly decreased in the treated groups. The kidney function test recorded more decreased values in the group treated with CWJ-MSCs than that treated with SWJ-MSCs. On the level of histopathology, the lesion scores recorded improvement of glomerular lesions and fibrosis in all experimental cases in the group treated with CWJ-MSCs while in the group treated with SWJ-MSCs the renal lesions improvement varied between experimental cases especially medullary fibrosis. Remarkable thickening of glomerular basement membrane and focal mononuclear cellular reaction were obvious in this group. NGAL, KIM-1genes decreased and EGFR gene increased in all treated groups indicating regeneration.
Conclusion:
SWJ- MSCs transplantation improve renal function tests and enhance tubular regeneration and tissue repair with degree less than CWJ-MSCS but failed to decrease fibrosis.
SWJ- MSCs transplantation in the induced CKD model incite interstitial mononuclear cells infiltration composed mainly of plasma cells and increase thickening of glomerular basement membrane, indicating immunological reaction occurrence.