Human adipose stromal cell therapy improves survival and reduces renal inflammation and capillary rarefaction in acute kidney injury

Jason A. Collett, Dmitry Traktuev, Purvi Mehrotra, Allison Crone, Stephanie Merfeld-Clauss, Keith L. March, David Basile

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Damage to endothelial cells contributes to acute kidney injury (AKI) by causing impaired perfusion, while the permanent loss of the capillary network following AKI has been suggested to promote chronic kidney disease. Therefore, strategies to protect renal vasculature may impact both short-term recovery and long-term functional preservation post-AKI. Human adipose stromal cells (hASCs) possess pro-angiogenic and anti-inflammatory properties and therefore have been tested as a therapeutic agent to treat ischaemic conditions. This study evaluated hASC potential to facilitate recovery from AKI with specific attention to capillary preservation and inflammation. Male Sprague Dawley rats were subjected to bilateral ischaemia/reperfusion and allowed to recover for either two or seven days. At the time of reperfusion, hASCs or vehicle was injected into the suprarenal abdominal aorta. hASC-treated rats had significantly greater survival compared to vehicle-treated rats (88.7% versus 69.3%). hASC treatment showed hastened recovery as demonstrated by lower creatinine levels at 48 hrs, while tubular damage was significantly reduced at 48 hrs. hASC treatment resulted in a significant decrease in total T cell and Th17 cell infiltration into injured kidneys at 2 days post-AKI, but an increase in accumulation of regulatory T cells. By day 7, hASC-treated rats showed significantly attenuated capillary rarefaction in the cortex (15% versus 5%) and outer medulla (36% versus 18%) compared to vehicle-treated rats as well as reduced accumulation of interstitial alpha-smooth muscle actin-positive myofibroblasts. These results suggest for the first time that hASCs improve recovery from I/R-induced injury by mechanisms that contribute to decrease in inflammation and preservation of peritubular capillaries.

Original languageEnglish (US)
JournalJournal of Cellular and Molecular Medicine
DOIs
StateAccepted/In press - 2017

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Stromal Cells
Cell- and Tissue-Based Therapy
Acute Kidney Injury
Inflammation
Kidney
Survival
Reperfusion
Th17 Cells
Myofibroblasts
Abdominal Aorta
Regulatory T-Lymphocytes
Chronic Renal Insufficiency
Smooth Muscle
Sprague Dawley Rats
Actins
Creatinine
Anti-Inflammatory Agents
Therapeutics
Ischemia
Endothelial Cells

Keywords

  • Acute kidney injury
  • Adipose stem cells
  • Inflammation
  • Stromal cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Cite this

Human adipose stromal cell therapy improves survival and reduces renal inflammation and capillary rarefaction in acute kidney injury. / Collett, Jason A.; Traktuev, Dmitry; Mehrotra, Purvi; Crone, Allison; Merfeld-Clauss, Stephanie; March, Keith L.; Basile, David.

In: Journal of Cellular and Molecular Medicine, 2017.

Research output: Contribution to journalArticle

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