Elsevier

American Heart Journal

Volume 162, Issue 6, December 2011, Pages 973-980
American Heart Journal

Trial Design
Developing mechanistic insights into cardiovascular cell therapy: Cardiovascular Cell Therapy Research Network Biorepository Core Laboratory rationale

https://doi.org/10.1016/j.ahj.2011.05.024Get rights and content

Moderate improvements in cardiac performance have been reported in some clinical settings after delivery of bone marrow mononuclear cells to patients with cardiovascular disease. However, mechanistic insights into how these cells impact outcomes are lacking. To address this, the National Heart, Lung and Blood Institute (NHLBI) Cardiovascular Cell Therapy Research Network (CCTRN) established a Biorepository Core for extensive phenotyping and cell function studies and storing bone marrow and peripheral blood for 10 years. Analyzing cell populations and cell function in the context of clinical parameters and clinical outcomes after cell or placebo treatment empower the development of novel diagnostic and prognostics. Developing such biomarkers that define the safety and efficacy of cell therapy is a major Biorepository aim.

Section snippets

Methods

Details of the trial protocols are published elsewhere.20, 21, 23, 24 All studies were conducted according to the CCTRN guidelines with approval of institutional review boards of each participating institution, and each patient provided written informed consent.

Effect of shipping temperature on cell viability and phenotype

Shipping with refrigerated (4°C) packs maintained both cell number and overall viability at levels similar to control samples stored at 4°C for 24 hours (Figure 4, A). The temperatures of the samples were (1) 8°C for 4°C stored samples; (2) 7°C to 14°C for samples shipped with refrigerated packs; (3) usually <5°C for samples shipped with frozen packs; and (4) 19°C to 22°C for room temperature samples. Specimens shipped with frozen packs showed a significant decrease in viability compared with

Discussion

One of the most valuable assets in the cardiovascular field is the Framingham Heart Study data set from which several important diagnostic and prognostic markers have emerged over the past 60 years.29 Yet, to date, it is not possible to correlate the important prognostic and diagnostic data gathered from Framingham patients with one of the more potent therapies envisioned—stem cell–mediated recovery after myocardial or vascular injury. The heterogeneity of clinical outcomes after cell therapy (

Conclusions

Creation of a Biorepository Core Laboratory for characterization of biologics is feasible in a network. Within the United States, samples can be shipped nationally and physiologically relevant measurements can be made in a timely manner from shipped samples. To maximize the use of these cell samples, they should be shipped at 4°C to avoid freezing, and elapsed time from blood draw to processing should be 24 to 48 hours. Adhering to these established SOPs reduces variability in cell phenotype

Disclosures

Conflict of interest disclosure: The authors declare no conflicts of interest.

Acknowledgements

We thank the CCTRN site principal investigators, the site research coordinators, and the patients. We also wish to thank Paul Champoux at the University of Minnesota for his flow cytometry support and advice.

The authors are solely responsible for the design and conduct of this study, all study analyses, and the drafting and editing of the paper and its final contents.

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  • Cited by (0)

    This study was supported by research grants from the NIH NHLBI (U01 HL087318-01) and by the Production Assistance for Cellular Therapies (PACT) N01-HB-37164 and HHSN268201000008C. The University of Minnesota flow cytometer, a Masonic Cancer Center shared resource, was supported in part by grant NIH P30 CA77598.

    g

    For the Cardiovascular Cell Therapy Research Network (CCTRN).

    h

    Denotes Biorepository codirectors.

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