Transplantation of bone marrow-derived MSCs improves cisplatinum-induced renal injury through paracrine mechanisms

Kang Cheng, Partab Rai, Andrei Plagov, Xiqian Lan, Dileep Kumar, Divya Salhan, Shabina Rehman, Ashwani Malhotra, Kuldeep Bhargava, Christopher J. Palestro, Sanjeev Gupta, Pravin C. Singhal

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Mesenchymal stem cells (MSCs) have been reported to preserve renal function in various models of acute kidney injury (AKI). Different routes were used to transplant MSCs but the role of cell transplantation routes in directing outcomes has been unknown. In the present study, we evaluated organ bio-distributions of transplanted MSCs, and correlated survival of transplanted cells with outcomes in mice with cisplatinum-induced AKI. We found that after intravenous administration, MSCs were largely localized in pulmonary capillaries and only a minute fraction of MSCs entered kidneys and the cells survived only transiently. Therefore, we also transplanted MSCs via intraperitoneal and renal subcapsular routes. Transplanted MSCs survived longer in peritoneal cavity and renal subcapsular space. Interestingly, when MSC transplantation was followed by cisplatinum-induced AKI, renal morphology and renal functions were better preserved, irrespective of the cell transplantation route. As transplanted MSCs did not migrate to kidneys from either peritoneal cavity or renal subcapsular space, this finding suggested that migration of cells was not required for the beneficial response. The possibility of indirect mechanisms was confirmed when administration of the conditioned medium from MSCs also protected renal tubular cells from cisplatinum-induced cytotoxicity. We identified presence of over forty regulatory cytokines in the conditioned medium obtained from MSCs. Since paracrine factors released by transplanted cells accounted for improvements, it appears that the route of cell transplantation is not critical for realizing benefits of cell therapy with MSCs in AKI. Studies of specific cytokines secreted by MSCs will help to obtain new therapeutic mechanisms for renal protection.

Original languageEnglish (US)
Pages (from-to)466-473
Number of pages8
JournalExperimental and Molecular Pathology
Volume94
Issue number3
DOIs
StatePublished - Jun 2013

Fingerprint

Stem cells
Bone Marrow Transplantation
Mesenchymal Stromal Cells
Bone
Kidney
Wounds and Injuries
Acute Kidney Injury
Cell Transplantation
Peritoneal Cavity
Conditioned Culture Medium
Mesenchymal Stem Cell Transplantation
Cytokines
Transplantation (surgical)
Transplants
Cell- and Tissue-Based Therapy
Cytotoxicity
Intravenous Administration
Cell Movement
Cell Survival
Cells

Keywords

  • Acute kidney injury
  • Cisplatinum
  • Mesenchymal stem cells

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Pathology and Forensic Medicine

Cite this

Transplantation of bone marrow-derived MSCs improves cisplatinum-induced renal injury through paracrine mechanisms. / Cheng, Kang; Rai, Partab; Plagov, Andrei; Lan, Xiqian; Kumar, Dileep; Salhan, Divya; Rehman, Shabina; Malhotra, Ashwani; Bhargava, Kuldeep; Palestro, Christopher J.; Gupta, Sanjeev; Singhal, Pravin C.

In: Experimental and Molecular Pathology, Vol. 94, No. 3, 06.2013, p. 466-473.

Research output: Contribution to journalArticle

Cheng, K, Rai, P, Plagov, A, Lan, X, Kumar, D, Salhan, D, Rehman, S, Malhotra, A, Bhargava, K, Palestro, CJ, Gupta, S & Singhal, PC 2013, 'Transplantation of bone marrow-derived MSCs improves cisplatinum-induced renal injury through paracrine mechanisms', Experimental and Molecular Pathology, vol. 94, no. 3, pp. 466-473. https://doi.org/10.1016/j.yexmp.2013.03.002
Cheng, Kang ; Rai, Partab ; Plagov, Andrei ; Lan, Xiqian ; Kumar, Dileep ; Salhan, Divya ; Rehman, Shabina ; Malhotra, Ashwani ; Bhargava, Kuldeep ; Palestro, Christopher J. ; Gupta, Sanjeev ; Singhal, Pravin C. / Transplantation of bone marrow-derived MSCs improves cisplatinum-induced renal injury through paracrine mechanisms. In: Experimental and Molecular Pathology. 2013 ; Vol. 94, No. 3. pp. 466-473.
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