The present disclosure relates to methods of preparing cell-based products for human consumption, in particular, from populations of such cell types as hepatocytes, adipocytes, myoblasts, and/or fibroblasts.

Methods for generating high-yield, high-purity epicardial cells are described. Wnt/β-catenin signaling is first activated in human cardiac progenitor cells, by, for example, inhibiting Gsk-3 to induce differentiation into epicardial cells. Methods for long-term in vitro maintenance of human cardiac progenitor cell-derived epicardial cells and method comprising chemically defined, xeno-free, and albumin-free culture conditions are also provided.

Provided herein are recombinant cardiomyocytes and cardiomyocyte cell lines expressing human Ether-a-go-go Related Gene (hERG) potassium ion channel, including, for example, stable cell lines, that comprise a transfected or transduced nucleic acid sequence encoding hERG. Also provided herein are methods of using the recombinant cardiomyocytes and cardiomyocyte cell lines expressing hERG for screening compounds for cardiotoxicity, including methods for determining the activity of compounds to inhibit hERG.

Disclosed herein are methods and compositions for generating pacemaker cells from non-pacemaker cardiomyocytes. For example, the method includes the step of culturing the non-pacemaker cardiomyocytes with silk fibroin so that the silk fibroin induces the transformation of at least a portion thereof into pacemaker cells.

Disclosed are microcapsule compositions and methods for encapsulating living cells. The methods include a microencapsulation approach to isolate and culture high-quality stem cells, including human iPSCs, cancer stem cells, cardiac stem cells, and the like. The microencapsulation methods are inspired by the development of blastomeres into a blastocyst within the Zona pellucida of the human female reproductive system. The bioinspired methods include encapsulation of blastomere-like cell clusters in a Zona-like microcapsule including a miniaturized hyaluronic acid-rich core and a semipermeable hydrogel shell. The cell clusters are subsequently cultured to form highly pluripotent spheroids with improved cell quality, homogeneity, and viability. Methods of use of said microcapsules are also disclosed including therapeutic uses related to human iPSC-based personalized medicines.

Disclosed herein are methods for generating mature cardiomyocytes and compositions including mature cardiomyocytes. Also disclosed herein are methods for enhancing maturation of quiescent cardiomyocytes and compositions including mature quiescent cardiomyocytes.

The purpose of the present invention is to provide: detergent-free decellularization method of xenogenic biological tissues for human body surgery, in which the pericardium, blood vessels, other membrane-like biological tissues, and the like are decellularized so as to have resistance to mechanical property loss, mineralization and immune reactivity; and decellularized tissue. Decellularized tissue, according to the present invention, when compared to untreated tissue, has greater calcification reduction in vivo, blood compatibility and biocompatibility improvement, tissue thickness reduction, and increases in tensile strength, kink resistance and the like.

Animal cells, notably adult fibroblasts, are advantageously reprogrammed in direct lineage reprogramming methods using defined factors to produce proliferative and multipotent induced cardiac progenitor cells (iCPC). The iCPC thus produced can be differentiated under suitable differentiation conditions to cardiac lineage cells including cardiomyocytes, smooth muscle cells, and endothelial cells, as evidenced by expression of lineage specific markers. Sets of factors effective in combination to reprogram the fibroblasts can include a set that includes some or all of 5 factors (Mesp1, Baf60c, Nkx2.5, Gata4, Tbx5), a set that includes some or all of 11 factors (Mesp1, Mesp2, Gata4, Gata6, Baf60c, SRF, Isl1, Nkx2.5, Irx4, Tbx5, Tbx20), a set that includes some or all of 18 factors (T, Mesp1, Mesp2, Tbx5, Tbx20, Isl1, Gata4, Gata6, Irx4, Nkx2.5, Hand1, Hand2, Tbx20, Tbx18, Tip60, Baf60c, SRF, Hey2), and a set that includes some or all of 22 factors (T, Mesp1, Mesp2, Tbx5, Tbx20, Isl1, Gata4, Gata6, Irx4, Nkx2.5, Hand1, Hand2, Tbx20, Tbx18, Tip60, Baf60c, SRF, Hey2, Oct4, Klf4, Sox2, L-myc).

The present invention relates in part to methods for producing tissue-specific cells from patient samples, and to tissue-specific cells produced using these methods. Methods for reprogramming cells using RNA are disclosed. Therapeutics comprising cells produced using these methods are also disclosed.

The present invention provides a new method for producing Engineered Heart Muscle (EHM) under chemically fully defined conditions all compatible with GMP regulations. The resulting human myocardium generates force and shows typical heart muscle properties.