New Paradigms in Cell Therapy: Repeated Dosing, Intravenous Delivery, Immunomodulatory Actions, and New Cell Types

Several human studies show positive signals, while research methods and sample sizes continue to develop.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Perhaps the most important advance in the field of cell therapy for heart disease has been the recognition that all stem/progenitor cells (both adult and embryonic) fail to engraft in the heart to a significant extent and thus work via paracrine mechanisms. This fundamental advance has led to 4 new paradigms that are discussed in this review and that may importantly shape, or even revolutionize, the future of the field: (1) repeated cell therapy, (2) intravenous cell therapy, (3) immunomodulatory actions of cell therapy, and (4) new cell types. Because virtually all of our current knowledge of cell therapy is predicated on the effects of a single cell dose, the idea that the full therapeutic effects of a cell product require repeated doses is disruptive and has far-reaching implications. For example, inadequate dosing (single-dose protocols) may be responsible, at least in part, for the borderline or disappointing results obtained to date in clinical trials; furthermore, future studies (both preclinical and clinical) may need to incorporate repeated cell administrations. Another disruptive idea, supported by emerging preclinical and clinical evidence, is that intravenously injected cells can produce beneficial effects on the heart, presumably via release of paracrine factors in extracardiac organs or endocrine factors into the systemic circulation. Intravenous administration wo

Evidence level

Several human studies show positive signals, while research methods and sample sizes continue to develop.

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