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

Zierold, Claudia; Carlson, Marjorie; Obodo, Udochukwu; Wise, Elizabeth; Piazza, Victor A.; Meeks, Marshall W.; Vojvodic, Rachel W.; Baraniuk, Sarah; Henry, Timothy D.; Gee, Adrian P.; Ellis, Stephen G.; Moyé, Lemuel A.; Pepine, Carl J.; Cogle, Christopher R.; Taylor, Doris A.

doi:10.1016/j.ahj.2011.05.024

Cited by 17 publications

(29 citation statements)

References 29 publications

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“…8, 9 These analyses were pre-specified in the Ancillary Functional Studies for the CCTRN protocol. The design and rationale of the CCTRN TIME trial and the CCTRN Biorepository are described elsewhere.…”

Section: Methodsmentioning

confidence: 99%

“…The design and rationale of the CCTRN TIME trial and the CCTRN Biorepository are described elsewhere. 9, 10 Briefly, CCTRN TIME was a multicenter, controlled, randomized, double-blind trial conducted at 5 clinical centers, their satellite facilities, and a data coordinating center. The trial protocol was approved by the local institutional review boards at each center, and participants provided written informed consent.…”

Section: Methodsmentioning

confidence: 99%

“…With permission, the excess BMCs were sent to the CCTRN Biorepository for phenotype and functional analyses and storage. 9 …”

Section: Methodsmentioning

confidence: 99%

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Bone Marrow Characteristics Associated With Changes in Infarct Size After STEMI

Schutt

Trachtenberg

Cooke

et al. 2015

Circulation Research

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Rationale Despite significant interest in bone marrow mononuclear cell (BMC) therapy for ischemic heart disease, current techniques have resulted in only modest benefits. However, select patients have shown improvements after autologous BMC therapy, but the contributing factors are unclear. Objective The purpose of this study was to identify BMC characteristics associated with a reduction in infarct size following STEMI. Methods and Results This prospective study comprised patients consecutively enrolled in the CCTRN TIME trial who agreed to have their BMCs stored and analyzed at the CCTRN Biorepository. Change in infarct size between baseline (3 days after percutaneous coronary intervention) and 6-month follow-up was measured by cardiac magnetic resonance imaging (cMRI). Infarct-size measurements and BMC phenotype and function data were obtained for 101 patients (mean age, 56.5 years; mean screening ejection fraction, 37%; mean baseline cMRI ejection fraction, 45%). At 6 months, 75 patients (74.3%) showed a reduction in infarct size (mean change, -21.0%±17.6%). Multiple regression analysis indicated that infarct size reduction was greater in patients who had a larger percentage of CD31+ BMCs (P=0.046) and in those with faster BMC growth rates in CFU-Hill and ECFC functional assays (P=0.033 and P=0.032, respectively). Conclusions This study identified BMC characteristics associated with a better clinical outcome in patients with STEMI and highlighted the importance of endothelial precursor activity in regenerating infarcted myocardium. Furthermore, it suggests that for these STEMI patients, myocardial repair was more dependent on baseline BMC characteristics than on whether the patient underwent intracoronary BMC transplantation. Trial Registration clinicaltrials.gov Identifier: NCT00684021

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Bone Marrow Characteristics Associated With Changes in Infarct Size After STEMI

Schutt

Trachtenberg

Cooke

et al. 2015

Circulation Research

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“…(13, 14) Selected cell populations from the bone marrow enriched for angiogenic activities may provide a superior therapeutic effect (15) A subtype of hematopoietic progenitor cells has been isolated based on the presence of the cytosolic enzyme ALDH, a marker for stem and progenitor cells (Lin- CD34+CD38−). (16) This subpopulation of progenitor cells, called ALDH br cells, represents about 1% of total BMMNCs and contains a heterogeneous mixture of cell types thought to be needed for ischemic repair, including hematopoietic, endothelial, and mesenchymal progenitor cells.…”

Section: Introductionmentioning

confidence: 99%

Rationale and Design for PACE: Patients with Intermittent Claudication Injected with ALDH Bright Cells

Perin¹,

Murphy

Cooke

et al. 2014

American Heart Journal

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Peripheral artery disease (PAD) is recognized as a public health issue because of its prevalence, functional limitations, and increased risk of systemic ischemic events. Current treatments for claudication, the primary symptom in PAD patients, have limitations. Cells identified usingcytosolic enzyme aldehyde dehydrogenase (ALDH) may benefit patients with severe PAD but has not been studied in patients with claudication. PACE is a randomized, double-blind, placebo-controlled clinical trial conducted by the Cardiovascular Cell Therapy Research Network (CCTRN) to assess the safety and efficacy of autologous bone marrow–derived ALDHbr cells delivered by direct intramuscular injections in 80 patients with symptom-limiting intermittent claudication. Eligible patients will have a significant stenosis or occlusion of infrainguinal arteries and a resting ankle-brachial index <0.90 and will be randomized 1:1 to cell or placebo treatment with a 1-year follow-up. The primary endpoints are the change in peak walking time and leg collateral arterial anatomy, calf muscle blood flow, and tissue perfusion as determined by magnetic resonance (MR) imaging at 6 months compared to baseline. The latter 3 measurements are new physiologic lower extremity tissue perfusion and PAD imaging-based endpoints that may help to quantify the biologic and mechanistic effects of cell therapy. This trial will collect important mechanistic and clinical information on the safety and efficacy of ALDHbr cells in patients with claudication and provide valuable insight into the utility of advanced MR imaging endpoints.

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“…We chose to add the ECFC assay in addition to several other ancillary studies as a means to quantify the proangiogenic activity of bone marrow mononuclear cells administered to patients. 2 …”

mentioning

confidence: 99%

Response to Letter Regarding Article, “A Detailed Analysis of Bone Marrow From Patients with Ischemic Heart Disease and Left Ventricular Dysfunction: BM CD34, CD11b and Clonogenic Capacity as Biomarkers for Clinical Outcomes”

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

Cited by 17 publications

References 29 publications

Bone Marrow Characteristics Associated With Changes in Infarct Size After STEMI

Bone Marrow Characteristics Associated With Changes in Infarct Size After STEMI

Rationale and Design for PACE: Patients with Intermittent Claudication Injected with ALDH Bright Cells

Response to Letter Regarding Article, “A Detailed Analysis of Bone Marrow From Patients with Ischemic Heart Disease and Left Ventricular Dysfunction: BM CD34, CD11b and Clonogenic Capacity as Biomarkers for Clinical Outcomes”

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