by screening using a high-throughput evaluation system relating to the promotion of the extracellular secretion of trimers of the causative proteins COL4A3/A4/A5, which decreased in the renal tissue of patients with Alport syndrome (AS), it was found that cyclosporin A has an effect of promoting extracellular secretion of trimers of type-IV collagen. From further studies, it was found that Alisporivir and NIM258, which do not inhibit calcineurin, also have an action to promote extracellular secretion of type-IV collagen. Furthermore, the present inventors have found that these actions are based on the cyclophilin D inhibitory mechanism, and have found a radical therapeutic agent for AS by inhibition of cyclophilin D. The present invention provides a composition and an AS therapeutic/prophylactic drug, which contain a cyclophilin D inhibitor as an active ingredient, for promoting the secretion of collagen trimers in cells having a mutated type-IV collagen gene.

The invention features polypeptides that include an extracellular ActRII chimera. In some embodiments, a polypeptide of the invention includes an extracellular ActRII chimera fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving weakness and atrophy of muscles, bone damage, low red blood cell levels (e.g., anemia or blood loss), low platelet levels (e.g., thrombocytopenia), low neutrophil levels (e.g., neutropenia), fibrosis, metabolic disorders, and/or pulmonary hypertension.

The present invention relates to improvement of the yield of skin-derived pluripotent precursor cells in induction of differentiation of stem cells to skin-derived pluripotent precursor cells. The present invention provides a method for preparing skin-derived pluripotent precursor cell comprising culturing a neural crest stem cells in the presence of at least one selected from the group consisting of laminin and a fragment thereof to differentiate the cells to skin-derived pluripotent precursor cells, wherein the laminin is at least one selected from the group consisting of laminin 111, laminin 121, laminin 332, laminin 421, laminin 511, laminin 521, and a variant thereof.

The present invention pertains to: the provision of a method for promoting skin wound healing and a composition to be used for promoting skin wound healing; the provision of a method useful for preventing or ameliorating ulcers and bedsores or a composition therefor; the provision of a method for preventing skin aging and a composition to be used for preventing skin aging; the provision of a composition useful for preventing or ameliorating skin damage caused by an anticancer agent; and, furthermore, the provision of a method for enhancing the regeneration ability of epidermal stem cells and a composition for enhancing the regeneration ability of epidermal stem cells. More specifically, use of a composition, said composition being characterized by comprising, as an active ingredient, a substance selected from the group consisting of a substance which induces or maintains the expression of COL17A1 in cells, a substance which inhibits the degradation of COL17A1 in cells, a substance which promotes the competitive amplification ability of epidermal stem cells, a substance which suppresses genomic stress or oxidative stress in cells and a substance which prevents DNA damage in cells, enables the promotion of skin wound healing, protection from an anticancer agent and prevention of skin aging. Thus, the regeneration ability of epidermal stem cells can be enhanced.

The present invention provides fusion polypeptides for inhibiting angiogenesis, fusion protein nanocages having peptides for inhibiting angiogenesis, and diagnostic and therapeutic (theranostic) uses thereof.

The present invention relates to heterotandem bicyclic peptide complexes which comprise a first peptide ligand, which binds to a component present on a cancer cell, conjugated via a linker to two or more second peptide ligands, which bind to a component present on an immune cell. The invention also relates to the use of said heterotandem bicyclic peptide complexes in preventing, suppressing or treating cancer.

An object of the present invention is to provide an angiogenic agent that can sufficiently exhibit an angiogenic effect due to mesenchymal stem cells in a state where the angiogenic agent does not allow permeation of host cells while being protected from immune rejection, and a method for method for manufacturing the same. According to the present invention, an angiogenic agent including a mesenchymal stem cell (A); and an immunoisolation membrane (B) that encloses the mesenchymal stem cell is provided.

The present disclosure provides synthetic collagen and methods of making and using synthetic collagen that include a synthetic collagen that facilitates wound closure comprising an isolated and purified triple helical backbone protein that facilitates wound closure comprising one or more alteration in a triple helical backbone protein sequence, that stabilize the isolated and purified triple helical backbone protein and does not disrupt an additional collagen ligand interaction; and one or more integrin binding motifs, wherein the isolated and purified triple helical backbone protein facilitates wound closure.

The present disclosure provides synthetic collagen and methods of making and using synthetic collagen that include a synthetic collagen that facilitates wound closure comprising an isolated and purified triple helical backbone protein that facilitates wound closure comprising one or more alteration in a triple helical backbone protein sequence, that stabilize the isolated and purified triple helical backbone protein and does not disrupt an additional collagen ligand interaction; and one or more integrin binding motifs, wherein the isolated and purified triple helical backbone protein facilitates wound closure.

The disclosure relates to integrin binding peptides, pharmaceutical compositions comprising the peptides and to uses thereof as therapeutic, diagnostic, imaging and targeting agents.