Role of Tumor Necrosis Factor Receptor 1 in Sex Differences of Stem Cell Mediated Cardioprotection

Courtney N. Zeller, Yue Wang, Troy A. Markel, Brent Weil, Aaron Abarbanell, Jeremy L. Herrmann, Megan L. Kelly, Arthur Coffey, Daniel R. Meldrum

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: Mesenchymal stem cells (MSCs) hold great therapeutic potential for the repair and regeneration of ischemic tissue, possibly through the release of beneficial paracrine factors. Sex differences have been observed in the paracrine function of MSCs. Female stem cells produce lower proinflammatory cytokines and higher levels of growth factors compared with their male counterparts. Ablation of tumor necrosis factor receptor 1 (TNFR1) increases protective growth factor production by male, but not by female, MSCs. We therefore hypothesized the following: (1) that female MSCs would improve myocardial recovery compared with male MSCs after ischemia-reperfusion injury (I/R); and (2) that MSCs isolated from TNFR1 knock out male, but not female, mice, would improve postischemic myocardial recovery compared with their wild type (WT) counterparts. Methods: Male adult Sprague-Dawley rat hearts were subjected to I/R by Langendorff isolated heart preparation. The MSCs were harvested from adult mice and cultured under normal conditions. Immediately prior to ischemia, one million MSCs were infused into the coronary circulation. Cardiac functional parameters were recorded continuously. Results: Pretreatment with MSCs from either sex significantly increased postischemic myocardial recovery as evidenced by improved left ventricular developed pressure, contractility, and rate of relaxation. Infusion with female MSCs was associated with a greater degree of myocardial recovery after I/R compared with male MSCs. The TNFR1 deficiency increased the degree of myocardial recovery associated with male MSCs, but not with female MSCs. No additional cardioprotection was observed when TNFR1 was ablated in female MSCs. Conclusion: Sex differences influence the cardioprotective effects of both WT and TNFR1 ablated MSCs.

Original languageEnglish
Pages (from-to)812-819
Number of pages8
JournalAnnals of Thoracic Surgery
Volume87
Issue number3
DOIs
StatePublished - Mar 2009

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Tumor Necrosis Factor Receptors
Mesenchymal Stromal Cells
Sex Characteristics
Stem Cells
Intercellular Signaling Peptides and Proteins
Receptors, Tumor Necrosis Factor, Type I
Coronary Circulation
Wounds and Injuries
Ventricular Pressure
Reperfusion Injury
Sprague Dawley Rats
Regeneration

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Pulmonary and Respiratory Medicine

Cite this

Role of Tumor Necrosis Factor Receptor 1 in Sex Differences of Stem Cell Mediated Cardioprotection. / Zeller, Courtney N.; Wang, Yue; Markel, Troy A.; Weil, Brent; Abarbanell, Aaron; Herrmann, Jeremy L.; Kelly, Megan L.; Coffey, Arthur; Meldrum, Daniel R.

In: Annals of Thoracic Surgery, Vol. 87, No. 3, 03.2009, p. 812-819.

Research output: Contribution to journalArticle

Zeller, CN, Wang, Y, Markel, TA, Weil, B, Abarbanell, A, Herrmann, JL, Kelly, ML, Coffey, A & Meldrum, DR 2009, 'Role of Tumor Necrosis Factor Receptor 1 in Sex Differences of Stem Cell Mediated Cardioprotection', Annals of Thoracic Surgery, vol. 87, no. 3, pp. 812-819. https://doi.org/10.1016/j.athoracsur.2008.12.033
Zeller, Courtney N. ; Wang, Yue ; Markel, Troy A. ; Weil, Brent ; Abarbanell, Aaron ; Herrmann, Jeremy L. ; Kelly, Megan L. ; Coffey, Arthur ; Meldrum, Daniel R. / Role of Tumor Necrosis Factor Receptor 1 in Sex Differences of Stem Cell Mediated Cardioprotection. In: Annals of Thoracic Surgery. 2009 ; Vol. 87, No. 3. pp. 812-819.
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abstract = "Background: Mesenchymal stem cells (MSCs) hold great therapeutic potential for the repair and regeneration of ischemic tissue, possibly through the release of beneficial paracrine factors. Sex differences have been observed in the paracrine function of MSCs. Female stem cells produce lower proinflammatory cytokines and higher levels of growth factors compared with their male counterparts. Ablation of tumor necrosis factor receptor 1 (TNFR1) increases protective growth factor production by male, but not by female, MSCs. We therefore hypothesized the following: (1) that female MSCs would improve myocardial recovery compared with male MSCs after ischemia-reperfusion injury (I/R); and (2) that MSCs isolated from TNFR1 knock out male, but not female, mice, would improve postischemic myocardial recovery compared with their wild type (WT) counterparts. Methods: Male adult Sprague-Dawley rat hearts were subjected to I/R by Langendorff isolated heart preparation. The MSCs were harvested from adult mice and cultured under normal conditions. Immediately prior to ischemia, one million MSCs were infused into the coronary circulation. Cardiac functional parameters were recorded continuously. Results: Pretreatment with MSCs from either sex significantly increased postischemic myocardial recovery as evidenced by improved left ventricular developed pressure, contractility, and rate of relaxation. Infusion with female MSCs was associated with a greater degree of myocardial recovery after I/R compared with male MSCs. The TNFR1 deficiency increased the degree of myocardial recovery associated with male MSCs, but not with female MSCs. No additional cardioprotection was observed when TNFR1 was ablated in female MSCs. Conclusion: Sex differences influence the cardioprotective effects of both WT and TNFR1 ablated MSCs.",
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AU - Weil, Brent

AU - Abarbanell, Aaron

AU - Herrmann, Jeremy L.

AU - Kelly, Megan L.

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