The CD133+ cell as advanced medicinal product for myocardial and limb ischemia
Dario Bongiovanni1, Beatrice Bassetti, Elisa Gambini
11 Laboratory of Vascular Biology and Regenerative Medicine , Centro Cardiologico Monzino-IRCCS, Milan, Italy .
Insights
CD133+ cells show promise in treating ischemic diseases by promoting new blood vessel growth and preventing cell death. Clinical trials indicate their potential as advanced cell products for heart and limb ischemia.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Vascular Biology
Background:
- Ischemic diseases are a leading cause of mortality and morbidity.
- Cell therapy, particularly using endothelial progenitor cells (ECPs), is a promising treatment strategy.
- A specific subpopulation, CD133+ ECPs, exhibits significant therapeutic potential.
Purpose of the Study:
- To review experimental and clinical data on CD133+ cells for myocardial and peripheral ischemia.
- To highlight the development of CD133+ cells as an advanced cell product (AMP).
Main Methods:
- Review of in vivo experimental evidence and clinical trial data.
- Analysis of CD133+ cell mechanisms in neovascularization.
- Characterization of CD133+ cell manufacturing as an AMP.
Main Results:
- CD133+ cells demonstrate pro-angiogenic and antiapoptotic effects in ischemic tissues.
- Evidence supports direct differentiation and paracrine signaling by CD133+ cells.
- Clinical trials show beneficial effects of CD133+ cell infusion in ischemic conditions.
Conclusions:
- CD133+ cells possess significant potential for reversing ischemia.
- The manufacturing of CD133+ cells is advancing as a therapeutic AMP.
- Further development of CD133+ cell therapy is warranted for ischemic diseases.
Abstract:
Ischemic diseases are the major cause of death and morbidity in Western countries. In the last decade, cell therapy has been suggested to be a promising treatment both in acute/chronic myocardial and peripheral ischemia. Different cell lineages have been tested, including endothelial progenitor cells. A subpopulation of bone marrow-derived immature ECPs, expressing the highly conserved stem cell glycoprotein antigen prominin-1 or CD133 marker, was shown to possess pro-angiogenic and antiapoptotic effects on ischemic tissues. The mechanisms implicated in CD133+ cells ability to contribute to neovascularization processes have been attributed to their ability to directly differentiate into newly forming vessels and to indirectly activate pro-angiogenic signaling by paracrine mechanisms. A large body of in vivo experimental evidences has demonstrated the potential of CD133+ cells to reverse ischemia. Moreover, several clinical trials have reported promising beneficial effects after infusion of autologous CD133+ into ischemic heart and limbs exploiting various delivery strategies. These trials have contributed to characterize the CD133+ manufacturing process as an advanced cell product (AMP). The aim of this review is to summarize available experimental and clinical data on CD133+ cells in the context of myocardial and peripheral ischemia, and to focus on the development of the CD133+ cell as an anti-ischemic AMP.


