TNF receptor 2, not TNF receptor 1, enhances mesenchymal stem cell-mediated cardiac protection following acute ischemia

Megan L. Kelly, Meijing Wang, Paul R. Crisostomo, Aaron M. Abarbanell, Jeremy L. Herrmann, Brent R. Weil, Daniel R. Meldrum

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Mesenchymal stem cells (MSCs) may improve myocardial function after I/R injury via paracrine effects, including the release of growth factors. Genetic modification of MSCs is an appealing method to enhance MSC paracrine action. Ablation of TNF receptor 1 (TNFR1), but not TNFR2, increases MSC growth factor production. In this study, therefore, we hypothesized that 1) preischemic infusion of MSCs derived from TNFR1 knockout (TNFR1KO) mice will further improve myocardial functional recovery and that 2) TNFR2KO and TNFR1/2KO will abolish MSC-mediated protection in the heart after I/R injury. Mesenchymal stem cells were harvested from adult C57BL/6J (wild-type 1 [WT1]), B6129SF2 (WT2), TNFR1KO, TNFR2KO, and TNFR1/2KO mice. Mesenchymal stem cells were cultured and adopted for experiments after passage 3. Isolated hearts from adult male Sprague-Dawley rats were subjected to 25 min of ischemia and 40 min of reperfusion (Langendorff model), during which time myocardial function was continuously monitored. Before ischemia, 1 mL of vehicle or 1 × 106 MSCs/mL from WT1, WT2, TNFR1KO, TNFR2KO, or TNFR1/2KO was infused into the hearts (n = 4-6 per group). Treatment of C57BL/6J mice with MSC before ischemia significantly increased cardiac function. TNFR1 knockout MSCs demonstrated greater cardioprotection when compared with WT MSCs after I/R, as exhibited by improved left ventricular developed pressure and ±dp/dt. However, infusion of MSCs from TNFR2KO and TNFR1/2KO mice either offered no benefit or decreased MSC-mediated cardiac functional recovery in response to I/R when compared with WT MSCs. TNFR1 signaling may damage MSC paracrine effects and decrease MSC-mediated cardioprotection, whereas TNFR2 likely mediates beneficial effects in MSCs.

Original languageEnglish
Pages (from-to)602-607
Number of pages6
JournalShock
Volume33
Issue number6
DOIs
StatePublished - Jun 2010

Fingerprint

Tumor Necrosis Factor Receptors
Mesenchymal Stromal Cells
Ischemia
Receptors, Tumor Necrosis Factor, Type II
Receptors, Tumor Necrosis Factor, Type I
Intercellular Signaling Peptides and Proteins
Stem Cell Factor
Cytoprotection
Wounds and Injuries
Ventricular Pressure

Keywords

  • Bone marrow cells
  • Ischemia/reperfusion
  • Myocardial function
  • Paracrine effects

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Kelly, M. L., Wang, M., Crisostomo, P. R., Abarbanell, A. M., Herrmann, J. L., Weil, B. R., & Meldrum, D. R. (2010). TNF receptor 2, not TNF receptor 1, enhances mesenchymal stem cell-mediated cardiac protection following acute ischemia. Shock, 33(6), 602-607. https://doi.org/10.1097/SHK.0b013e3181cc0913

TNF receptor 2, not TNF receptor 1, enhances mesenchymal stem cell-mediated cardiac protection following acute ischemia. / Kelly, Megan L.; Wang, Meijing; Crisostomo, Paul R.; Abarbanell, Aaron M.; Herrmann, Jeremy L.; Weil, Brent R.; Meldrum, Daniel R.

In: Shock, Vol. 33, No. 6, 06.2010, p. 602-607.

Research output: Contribution to journalArticle

Kelly, ML, Wang, M, Crisostomo, PR, Abarbanell, AM, Herrmann, JL, Weil, BR & Meldrum, DR 2010, 'TNF receptor 2, not TNF receptor 1, enhances mesenchymal stem cell-mediated cardiac protection following acute ischemia', Shock, vol. 33, no. 6, pp. 602-607. https://doi.org/10.1097/SHK.0b013e3181cc0913
Kelly, Megan L. ; Wang, Meijing ; Crisostomo, Paul R. ; Abarbanell, Aaron M. ; Herrmann, Jeremy L. ; Weil, Brent R. ; Meldrum, Daniel R. / TNF receptor 2, not TNF receptor 1, enhances mesenchymal stem cell-mediated cardiac protection following acute ischemia. In: Shock. 2010 ; Vol. 33, No. 6. pp. 602-607.
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