Screening for Regenerative Therapy Responders in Heart Failure

Abstract

Risk of outcome variability challenges therapeutic innovation. Selection of the most suitable candidates is predicated on reliable response indicators. Especially for emergent regenerative biotherapies, determinants separating success from failure in achieving disease rescue remain largely unknown. Accordingly, (pre)clinical development programs have placed increased emphasis on the multi-dimensional decoding of repair capacity and disease resolution, attributes defining responsiveness. To attain regenerative goals for each individual, phenotype-based patient selection is poised for an upgrade guided by new insights into disease biology, translated into refined surveillance of response regulators and deep learning-amplified clinical decision support.

Regeneration of the heart: from molecular mechanisms to clinical therapeutics

“…Currently, a growing number of clinical trials [ 130 ] (see Bolli et al [ 129 ] for a comprehensive list of trials) and Meta-analyses [ 132 ] have greatly expanded the knowledge and potential choices of cell sources and interventions for heart disease, such as IMMNC-HF with bone marrow mononuclear cell [ 133 ]; LAPiS (NCT04945018), HEAL-CHF (NCT03763136) and NCT05223894 with human iPSC derived cardiomyocytes; NCT05147766 with UC-MSCs; NCT03797092 with adipose-derived stromal cell; and BioVAT-HF (NCT04396899) with engineered human myocardium. DREAM-HF, a phase III clinical trial, recruited 565 patients and upon completion will provide evidence in analyzing the efficiency of MSC injection as a heart failure treatment [ 14 , 134 , 135 ]. Recent studies show that human mesenchymal stromal cells and endothelial colony-forming cells reduce cardiomyocyte apoptosis, scar size, and adverse cardiac remodeling, compared to vehicle, in a pre-clinical model of acute myocardial infarction [ 136 ].…”

Mass Customized Outlook for Regenerative Heart Failure Care

“…The path to adoption in cardiology care will thus mandate a transdisciplinary effort bringing together multiple specialties to establish validated and fiscally responsible regenerative therapy guidelines across the discovery–development–delivery continuum [ 82 , 83 ]. In parallel with the focus on optimizing the regenerative product and associated procedures, standardization warrants the narrowing of “inter-patient” variability linked to the genetic make-up, comorbidities, disease pathobiology, and innate variance in responsiveness reflective of diversity among candidate recipients [ 84 ].…”

A primer on in vivo cell tracking using MRI

“…In stem cell applications, cells may be expected to differentiate and proliferate to create new tissue or repair an injury. Unfortunately, the number of surviving cells, migration to the desired therapeutic target, and extent of cell proliferation have been inconsistent, dependent partly on the patient ( 3 ) and manufacturing process ( 4 ), and can only be monitored by a non-invasive cellular imaging technique. Cell-tracking is an acknowledged, critical enabler in the development and eventual clinical translation of cell therapy.…”