Improved Targeting and Enhanced Retention of the Human, Autologous, Fibroblast-Derived, Induced, Pluripotent Stem Cells to the Sarcomeres of the Infarcted Myocardium with the Aid of the Bioengineered, Heterospecific, Tetravalent AntibodiesMarek Malecki*
Phoenix Biomolecular Engineering Foundation, San Francisco, CA, USA
- *Corresponding Author:
- Marek Malecki MD
PhD, Phoenix Biomolecular Engineering Foundation
San Francisco, CA, USA
E-mail: [email protected]
Received date April 14, 2013; Accepted date May 03, 2013; Published date May 06, 2013
Citation: Malecki M (2013) Improved Targeting and Enhanced Retention of the Human, Autologous, Fibroblast-Derived, Induced, Pluripotent Stem Cells to the Sarcomeres of the Infarcted Myocardium with the Aid of the Bioengineered, Heterospecific, Tetravalent Antibodies. J Stem Cell Res Ther 3:138. doi:10.4172/2157-7633.1000138
Copyright: © 2013 Malecki M. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Clinical trials, to regenerate the human heart injured by myocardial infarction, involve the delivery of stem cells to the site of the injury. However, only a small fraction of the introduced stem cells are detected at the site of the injury, merely two weeks after this therapeutic intervention. This significantly hampers the effectiveness of the stem cell therapy. To resolve the aforementioned problem, we genetically and molecularly bioengineered heterospecific, tetravalent antibodies (htAbs), which have both exquisite specificity and high affinity towards human, pluripotent, stem cells through the htAbs’ domains binding SSEA-4, SSEA-3, TRA-1-60, and TRA-1-81, as well as towards the injured cardiac muscle through the htAbs’ domains binding human cardiac myosin, α-actinin, actin, and titin. The cardiac tissue was acquired from the patients, who were receiving heart transplants. The autologous, human, induced, pluripotent stem cells (hiPSCs) were generated from the patients’ fibroblasts by non-viral delivery and transient expression of the DNA constructs for: Oct4, Nanog, Sox2, Lin28, Klf4, c-Myc. In the trials involving the htAbs, the human, induced, pluripotent stem cells anchored to the myocardial sarcomeres with the efficiency, statistically, significantly higher, than in the trials with non-specific or without antibodies (p < 0.001). Moreover, application of the htAbs resulted in cross-linking of the sarcomeric proteins to create the stable scaffolds for anchoring of the stem cells. Thereafter, these human, induced pluripotent stem cells differentiated into cardiomyocytes at their anchorage sites. By bioengineering of these novel heterospecific, tetravalent antibodies and using them to guide and to anchor the stem cells specifically to the stabilized sarcomeric scaffolds, we demonstrated the proof of concept in vitro for improving effectiveness of regenerative therapy of myocardial infarction and created the foundations for the trials in vivo.