Int J Stem Cells.  2019 Jul;12(2):304-314. 10.15283/ijsc18114.

Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Ischaemic-Reperfused Hearts in Adult Rats with Established Chronic Kidney Disease

• Hamed GM
• Morsy WE
• Abd-El Hamid MS
• Hassan AA
• Abu Zahra

• KMID: 2465900
• DOI: http://doi.org/10.15283/ijsc18114

Abstract

BACKGROUND AND OBJECTIVES
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are adult multipotent non-haematopoietic stem cells that have regeneration potential. The current study aimed to detect the ability of BM-MSCs to improve kidney and cardiac functions in adult rats with established chronic kidney disease.
METHODS
Rats were divided into sham-operated control, untreated sub totally nephrectomised and treated sub totally nephrectomised groups. Body weight, kidney and cardiac tissue weights, plasma creatinine and urea levels and arterial blood pressure were measured. ECG was recorded, and an in vitro isolated heart study was performed.
Results
Stem cell treatment decreased the elevated plasma creatinine and urea levels and decreased systolic, diastolic and mean arterial blood pressure values. These changes were accompanied by a decrease in glomerular hypertrophy with apparent normal renal parenchyma. Additionally, BM-MSCs shortened Q-To and Q-Tc intervals, all time to peak tension values, the half relaxation value at 30 min of reperfusion and the contraction time at 15 and 30 min of reperfusion. Moreover, stem cell treatment significantly increased the heart rate, QRS voltage, the peak tension at the 15- and 30-min reperfusion time points and the peak tension per left ventricle at the 30-min reperfusion time point compared to the pre-ischaemia baseline. BM-MSCs resolve inter muscular oedema and lead to the re-appearance of normal cardiomyocytes. This improvement occurs with the observations of BM-MSCs in renal and heart tissues.
CONCLUSIONS
BM-MSCs can attenuate chronic kidney disease progression and the associated cardiac electrophysiological and inotropic dysfunction.

Keyword

Chronic kidney disease; Nephrectomy; Bone marrow-derived stem cells; Isolated perfused heart study

MeSH Terms

Adult*
Animals
Arterial Pressure
Body Weight
Creatinine
Electrocardiography
Heart Rate
Heart Ventricles
Heart*
Humans
Hypertrophy
In Vitro Techniques
Kidney
Mesenchymal Stromal Cells*
Myocytes, Cardiac
Nephrectomy
Plasma
Rats*
Regeneration
Relaxation
Renal Insufficiency, Chronic*
Reperfusion
Stem Cells
Urea
Weights and Measures
Creatinine
Urea

Figure

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  Fig. 1 (A) Bone marrow-derived mesenchymal stem cells at culture days 1 and 8. (B) MSCs show negative expression of CD34 and positive expression of CD44 (f 400z×).

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  Fig. 2 Initial, 4-week and 8-week (a) systolic blood pressure (SBP), (b) diastolic blood pressure and (c) mean arterial blood pressure values in the three studied groups. *: Significant difference compared to their initial values as calculated by Student’s t-test for paired data. a: Significant difference compared to the sham-operated control (Sham) group as calculated by the LSD at p<0.05. b: Significant difference compared to the untreated subtotally nephrectomized (untreated STNx) group as calculated by the LSD at p<0.05.

• 

  Fig. 3 Results of the PCR assay for the male Y chromosome (sry) gene following 2% agarose gel electrophoresis and staining with ethidium bromide. M: DNA 100-bp marker, PC: positive PCR control (male rat genomic DNA), NC: negative PCR control (female rat genomic DNA). Lane 1~4: MSC-treated group, which was injected with mesenchymal stem cells (MSCs). Lane 5~8: Control and untreated groups that were not injected with male MSCs.

• 

  Fig. 4 Histopathological changes in 1-Control group: (A) Renal tissues (B) Cardiac muscles. 2-Untreated nephrectomised group (A) Renal tissues showing hypertrophy of the glomerular tufts and congestion of renal blood vessels (B) Cardiac muscle showing intramuscular oedema that caused dispersion of the cardiomyocytes. 3-MSCs treated group (A) Renal tissues showing apparent normal renal parenchyma (B) Cardiac muscles showing regained normal morphology (H&E ×400).

Reference

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