The structural basis of functional improvement in response to human umbilical cord blood stem cell transplantation in hearts with postinfarct lv remodeling

Yong Chen; Lei Ye; Jia Zhong; Xin Li; Chen Yan; Margaret P. Chandler; Steve Calvin; Feng Xiao; Mesfin Negia; Walter C. Low; Jianyi Zhang; Xin Yu

doi:10.3727/096368913X675746

The structural basis of functional improvement in response to human umbilical cord blood stem cell transplantation in hearts with postinfarct lv remodeling

Yong Chen, Lei Ye, Jia Zhong, Xin Li, Chen Yan, Margaret P. Chandler, Steve Calvin, Feng Xiao, Mesfin Negia, Walter C. Low, Jianyi Zhang, Xin Yu

Neurosurgery

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Cellular therapy for myocardial repair has been one of the most intensely investigated interventional strategies for acute myocardial infarction. Although the therapeutic potential of stem cells has been demonstrated in various studies, the underlying mechanisms for such improvements are poorly understood. In the present study, we investigated the long-term effects of stem cell therapy on both myocardial fiber organization and regional contractile function using a rat model of postinfarct remodeling. Human nonhematopoietic umbilical cord blood stem cells (nh-UCBSCs) were administered via tail vein to rats 2 days after infarct surgery. Animals were maintained without immunosuppressive therapy. In vivo and ex vivo MR imaging was performed on infarct hearts 10 months after cell transplantation. Compared to the age-matched rats exposed to the identical surgery, both global and regional cardiac functions of the nh-UCBSC-treated hearts, such as ejection fraction, ventricular strain, and torsion, were significantly improved. More importantly, the treated hearts exhibited preserved fiber orientation and water diffusivities that were similar to those in sham-operated control hearts. These data provide the first evidence that nh-UCBSC treatment may prevent/delay untoward structural remodeling in postinfarct hearts, which supports the improved LV function observed in vivo in the absence of immunosuppression, suggesting a beneficial paracrine effect occurred with the cellular therapy.

Original language	English (US)
Pages (from-to)	971-983,
Journal	Cell transplantation
Volume	24
Issue number	6
DOIs	https://doi.org/10.3727/096368913X675746
State	Published - 2015

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS: This work was supported by National Heart, Lung, and Blood Institute Grants R01 HL73315 and HL86935 (to X. Yu), HL50470, HL 67828, HL 95077, HL100407 (to J. Zhang), American Heart Association postdoctoral fellowship 09POST2080107 (to Y. Chen), and a Graduate School Grant-in-Aid from the University of Minnesota (to W. C. Low). The authors declare no conflicts of interest.

Keywords

Diffusion tensor mr imaging
Displacement encoding
Fiber architecture
Ischemic heart injury
Myocardial wall strain
Umbilical cord blood stem cells

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Chen, Y., Ye, L., Zhong, J., Li, X., Yan, C., Chandler, M. P., Calvin, S., Xiao, F., Negia, M., Low, W. C., Zhang, J., & Yu, X. (2015). The structural basis of functional improvement in response to human umbilical cord blood stem cell transplantation in hearts with postinfarct lv remodeling. Cell transplantation, 24(6), 971-983,. https://doi.org/10.3727/096368913X675746

The structural basis of functional improvement in response to human umbilical cord blood stem cell transplantation in hearts with postinfarct lv remodeling. / Chen, Yong; Ye, Lei; Zhong, Jia; Li, Xin; Yan, Chen; Chandler, Margaret P.; Calvin, Steve; Xiao, Feng; Negia, Mesfin; Low, Walter C.; Zhang, Jianyi; Yu, Xin.

In: Cell transplantation, Vol. 24, No. 6, 2015, p. 971-983,.

Research output: Contribution to journal › Article › peer-review

Chen, Yong ; Ye, Lei ; Zhong, Jia ; Li, Xin ; Yan, Chen ; Chandler, Margaret P. ; Calvin, Steve ; Xiao, Feng ; Negia, Mesfin ; Low, Walter C. ; Zhang, Jianyi ; Yu, Xin. / The structural basis of functional improvement in response to human umbilical cord blood stem cell transplantation in hearts with postinfarct lv remodeling. In: Cell transplantation. 2015 ; Vol. 24, No. 6. pp. 971-983,.

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title = "The structural basis of functional improvement in response to human umbilical cord blood stem cell transplantation in hearts with postinfarct lv remodeling",

abstract = "Cellular therapy for myocardial repair has been one of the most intensely investigated interventional strategies for acute myocardial infarction. Although the therapeutic potential of stem cells has been demonstrated in various studies, the underlying mechanisms for such improvements are poorly understood. In the present study, we investigated the long-term effects of stem cell therapy on both myocardial fiber organization and regional contractile function using a rat model of postinfarct remodeling. Human nonhematopoietic umbilical cord blood stem cells (nh-UCBSCs) were administered via tail vein to rats 2 days after infarct surgery. Animals were maintained without immunosuppressive therapy. In vivo and ex vivo MR imaging was performed on infarct hearts 10 months after cell transplantation. Compared to the age-matched rats exposed to the identical surgery, both global and regional cardiac functions of the nh-UCBSC-treated hearts, such as ejection fraction, ventricular strain, and torsion, were significantly improved. More importantly, the treated hearts exhibited preserved fiber orientation and water diffusivities that were similar to those in sham-operated control hearts. These data provide the first evidence that nh-UCBSC treatment may prevent/delay untoward structural remodeling in postinfarct hearts, which supports the improved LV function observed in vivo in the absence of immunosuppression, suggesting a beneficial paracrine effect occurred with the cellular therapy.",

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author = "Yong Chen and Lei Ye and Jia Zhong and Xin Li and Chen Yan and Chandler, {Margaret P.} and Steve Calvin and Feng Xiao and Mesfin Negia and Low, {Walter C.} and Jianyi Zhang and Xin Yu",

note = "Funding Information: ACKNOWLEDGMENTS: This work was supported by National Heart, Lung, and Blood Institute Grants R01 HL73315 and HL86935 (to X. Yu), HL50470, HL 67828, HL 95077, HL100407 (to J. Zhang), American Heart Association postdoctoral fellowship 09POST2080107 (to Y. Chen), and a Graduate School Grant-in-Aid from the University of Minnesota (to W. C. Low). The authors declare no conflicts of interest.",

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AU - Li, Xin

AU - Yan, Chen

AU - Chandler, Margaret P.

AU - Calvin, Steve

AU - Xiao, Feng

AU - Negia, Mesfin

AU - Low, Walter C.

AU - Zhang, Jianyi

AU - Yu, Xin

N1 - Funding Information: ACKNOWLEDGMENTS: This work was supported by National Heart, Lung, and Blood Institute Grants R01 HL73315 and HL86935 (to X. Yu), HL50470, HL 67828, HL 95077, HL100407 (to J. Zhang), American Heart Association postdoctoral fellowship 09POST2080107 (to Y. Chen), and a Graduate School Grant-in-Aid from the University of Minnesota (to W. C. Low). The authors declare no conflicts of interest.

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N2 - Cellular therapy for myocardial repair has been one of the most intensely investigated interventional strategies for acute myocardial infarction. Although the therapeutic potential of stem cells has been demonstrated in various studies, the underlying mechanisms for such improvements are poorly understood. In the present study, we investigated the long-term effects of stem cell therapy on both myocardial fiber organization and regional contractile function using a rat model of postinfarct remodeling. Human nonhematopoietic umbilical cord blood stem cells (nh-UCBSCs) were administered via tail vein to rats 2 days after infarct surgery. Animals were maintained without immunosuppressive therapy. In vivo and ex vivo MR imaging was performed on infarct hearts 10 months after cell transplantation. Compared to the age-matched rats exposed to the identical surgery, both global and regional cardiac functions of the nh-UCBSC-treated hearts, such as ejection fraction, ventricular strain, and torsion, were significantly improved. More importantly, the treated hearts exhibited preserved fiber orientation and water diffusivities that were similar to those in sham-operated control hearts. These data provide the first evidence that nh-UCBSC treatment may prevent/delay untoward structural remodeling in postinfarct hearts, which supports the improved LV function observed in vivo in the absence of immunosuppression, suggesting a beneficial paracrine effect occurred with the cellular therapy.

AB - Cellular therapy for myocardial repair has been one of the most intensely investigated interventional strategies for acute myocardial infarction. Although the therapeutic potential of stem cells has been demonstrated in various studies, the underlying mechanisms for such improvements are poorly understood. In the present study, we investigated the long-term effects of stem cell therapy on both myocardial fiber organization and regional contractile function using a rat model of postinfarct remodeling. Human nonhematopoietic umbilical cord blood stem cells (nh-UCBSCs) were administered via tail vein to rats 2 days after infarct surgery. Animals were maintained without immunosuppressive therapy. In vivo and ex vivo MR imaging was performed on infarct hearts 10 months after cell transplantation. Compared to the age-matched rats exposed to the identical surgery, both global and regional cardiac functions of the nh-UCBSC-treated hearts, such as ejection fraction, ventricular strain, and torsion, were significantly improved. More importantly, the treated hearts exhibited preserved fiber orientation and water diffusivities that were similar to those in sham-operated control hearts. These data provide the first evidence that nh-UCBSC treatment may prevent/delay untoward structural remodeling in postinfarct hearts, which supports the improved LV function observed in vivo in the absence of immunosuppression, suggesting a beneficial paracrine effect occurred with the cellular therapy.

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KW - Fiber architecture

KW - Ischemic heart injury

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