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.

摘要: Clinical trials, to regenerate the human heart injured by myocardial infarction, involve delivery of stem cells site injury. However, only a small fraction introduced are detected at injury, merely two weeks after this therapeutic intervention. This significantly hampers effectiveness cell therapy. To resolve aforementioned problem, we genetically and molecularly bioengineered heterospecific, tetravalent antibodies (htAbs), which have both exquisite specificity high affinity towards human, pluripotent, through htAbs’ domains binding SSEA-4, SSEA-3, TRA-1-60, TRA-1-81, as well cardiac muscle myosin, α-actinin, actin, titin. The tissue was acquired from patients, who were receiving transplants. autologous, induced, pluripotent (hiPSCs) generated patients’ fibroblasts non-viral transient expression DNA constructs for: Oct4, Nanog, Sox2, Lin28, Klf4, c-Myc. In trials involving htAbs, anchored sarcomeres with efficiency, statistically, higher, than in non-specific or without (p < 0.001). Moreover, application htAbs resulted cross-linking sarcomeric proteins create stable scaffolds for anchoring cells. Thereafter, these induced differentiated into cardiomyocytes their anchorage sites. By bioengineering novel using them guide anchor specifically stabilized scaffolds, demonstrated proof concept vitro improving regenerative therapy infarction created foundations vivo.