Disclosed herein are compositions and methods for cellular reprogramming. The compositions comprise one or more miRs and an activator of NFκB. Also provided are methods for enhancing or upregulating cardiomyocyte maturation in a cell or a subject and methods for inhibiting or downregulating cardiomyocyte maturation.

Provided herein are methods and devices related to inducing a population of self-renewing or senescent stem cells, to produce one or more beneficial factors for the treatment of a disease or disorder in an individual. Also provided are compositions and methods for inducing senescence, useful for inducing senescence in a population of stem cells, in order to produce one or more beneficial factors for the treatment of a disease or disorder in an individual. Methods and devices to control and customize the production of the beneficial factors for the requirements of a disease or disorder being treated are described. Also provided are factor production units for the production of the beneficial factors, and devices for the delivery of the beneficial factors to an individual in need.

Provided is a method for preparing a diabetic dog model by means of gene editing technology, a diabetic dog model prepared therefrom, as well as cells and issues thereof. The method comprises the following steps: (1) obtaining a dog fertilized egg cell, which comprises a point mutation in GCK gene, for a diabetic dog model by means of gene editing; and (2) transplanting the dog fertilized egg cell into one fallopian tube of a female dog, in which both fallopian tubes have been flushed, to prepare a diabetic dog model comprising a point mutation in GCK gene.

The present invention relates to a method for inducing megakaryocytic differentiation of hematopoietic stem/progenitor cells (HSPCs). The method comprises transferring into the HSPCs an effective amount of small RNAs. The HSPCs may differentiate into megakaryocytes in the absence of thrombopoietin (TPO) and/or without using megakaryocytic microparticles (MkMPs). The small RNAs may be micro RNAs (miRs) selected from the group consisting of miR-486, miR-22, miR-191, miR-181, miR-378, miR-26, let-7, miR-92, miR-126, miR-92, miR-21, miR-146, miR-181, and combinations thereof. For example, the small RNAs are miR-486 and miR-22. The small RNAs may be synthetic or isolated from cells. Also provided is a method for enhancing megakaryocytic differentiation of HSPCs cultured with megakaryocytic microparticles MkMPs in the presence of an effective amount of one or more exogenous small RNAs (e.g., miR-486).

The disclosure relates to immune cells for use in adoptive cell therapy that express an inhibitory receptor, useful for treating a disease or disorder, for example, cancer. The disclosure provides immune cells with reduced or eliminated HLA expression, that express an inhibitory receptor, methods of making same, shRNAs targeting HLA-A mRNA, and polynucleotides and vectors encoding same.

The present disclosure provides materials and methods for the delivery of therapeutic nucleic cells (and imaging agents) to tissues.

Induced overexpression of defined exogenous transcription factors (TFs), or alternatively treatment with specific pathway modulatory cocktails, can reprogram somatic cells to pluripotency or alternate cell states. A barrier to initiating reprogramming lies in the starting cell's molecular identity, enforced by lineage-instructive TFs. However, it remained unclear whether repression of such somatic lineage-defining TFs of the starting cell in the absence of exogenous TFs is sufficient to induce cell reprogramming Using an intra-species somatic cell hybrid model, SNAI2 and PRRX1 were identified as the most critical determinants of mesenchymal commitment in rat embryonic fibroblasts (REFs) and demonstrate that siRNA-mediated transient knockdown of these individual factors is adequate to convert REFs into functional adipocytes, chondrocytes or osteocytes without requiring the provision of exogenous TFs. Additionally, it was shown that siRNA-mediated transient knockdown of SNAI2 alone, in the absence of exogenous TFs, is sufficient to transform REFs to a dedifferentiated pluripotent stem-like cell (dPSC) state that forms embryoid bodies and is capable of triple germ layer differentiation. These results establish for the first time that transient repression of a single somatic lineage-defining TF can effectively induce transdifferentiation to alternative somatic cell states or dedifferentiation to dPSCs in the absence of exogenous TFs or small molecule cocktails.

The invention provides oligonucleotides complementary to a non-coding chimeric mitochondrial RNA as well as compositions and kits comprising the same, and their use in treating and preventing metastasis or relapse of a cancer in an individual previously treated for cancer with a therapy. The invention also provides oligonucleotides complementary to a non-coding chimeric mitochondrial RNA as well as compositions and kits comprising the same, and their use in treating a refractory cancer (e.g., a refractory HPV-associated cancer).

The invention is situated in the field of cancer immunotherapy and more specifically the maturation of antigen-presenting cells in order to enhance their potency to induce an immune response.

The purpose of the present invention is to provide a chondrocyte culture with high tissue regeneration ability. This purpose is met by a method involving a step in which a cell population separated from cartilage tissue is cultured on a thermoreversible polymer.