Can mobilization of bone marrow stem cells be an alternative regenerative therapy to stem cell injection in a rat model of chronic kidney disease?

Physiol Rep. 2022 Sep;10(17):e15448. doi: 10.14814/phy2.15448.

Abstract

Chronic kidney disease (CKD) is a priority health problem affecting 36% of Egyptians. Adipose-derived mesenchymal stem cells (ADMSCs) have multidifferentiation capacity and the ability to restore several types of cells including damaged renal cells. Granulocyte colony-stimulating factor (G-CSF) is known to mobilize hematopoietic stem cells from bone marrow to the peripheral circulation. The aim of this study was to compare the effect of endogenous CD34+ cells mobilization and exogenous ADMSCs administration in the treatment of a rat model of adriamycin (ADR)-induced CKD. A total of 48 male albino rats of the local strain (200 ± 50 g) were equally divided into four groups: control negative, ADR (control positive), ADMSCs group, and G-CSF group. Six rats from each group were sacrificed after 4 weeks and the other 6 after 12 weeks. Renal function was assessed frequently by measuring serum creatinine, albumin, urea, 24-h urinary protein level, and hemoglobin level throughout the study. Oxidative stress markers malondialdehyde (MDA) and total antioxidant (TAO) were measured on day 28. CD-34+ cell percentage was measured on day 9. After the sacrification of the rats, kidneys were removed for histopathological assessment. Results revealed that both ADMSCs and G-CSF significantly improved serum creatinine, albumin, urea, 24-h urinary protein level, and histopathological damage score, with the G-CSF-treated group showing better improvement in 24-h urinary protein level, serum albumin, and histopathological damage score compared with ADMSCs-treated group. The G-CSF group also had significantly higher levels of CD34+ cells. Oxidative stress markers (MDA and TAO) levels were significantly improved with both therapies. We conclude that mobilization of endogenous hematopoietic stem cells by G-CSF is more effective than exogenously injected ADMSCs in protecting the kidneys against AD-induced toxicity.

Keywords: CD34+ stem cells; adipose tissue-derived mesenchymal stem cells; adriamycin; chronic kidney disease; granulocyte colony-stimulating factor; malondialdehyde.

MeSH terms

  • Albumins
  • Animals
  • Bone Marrow Cells
  • Creatinine
  • Disease Models, Animal
  • Doxorubicin / pharmacology
  • Granulocyte Colony-Stimulating Factor* / pharmacology
  • Granulocyte Colony-Stimulating Factor* / therapeutic use
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells* / metabolism
  • Male
  • Rats
  • Renal Insufficiency, Chronic* / chemically induced
  • Renal Insufficiency, Chronic* / therapy
  • Urea

Substances

  • Albumins
  • Granulocyte Colony-Stimulating Factor
  • Doxorubicin
  • Urea
  • Creatinine