Methods of generating conditionally active proteins that target senescent cells and which are conditionally active in an extracellular environment of a senescent cell. The methods include discovery methods using libraries of evolved proteins and assays employing physiological concentrations of components of bodily fluids. Also disclosed are conditionally active proteins for killing or removing senescent cells, pharmaceutical compositions employing these conditionally active proteins and methods for treatment of age-related diseases, conditions or disorders using same. The conditionally active proteins may be further evolved, conjugated to other molecules, masked, reduced in activity by attaching a cleavable moiety.

Compositions and methods for domain-specific targeting of CD206 are presented in which selected agents bind to the carbohydrate recognition domain 4 (CRD4) and carbohydrate recognition domain 5 (CRD5) of CD206. In certain aspects of the inventive subject matter, binding is specific, leads to a conformational change of CD206, and will induce phagocytosis in tumor associated macrophages and/or M2 macrophage cell death.

Ex vivo cell-based living biosensors, methods of imaging and identifying cell types and/or cell phenotypes, and uses of the systems and methods are provided.

An object of the present invention is to provide novel apoptosis inhibitors and therapeutic agents for inner ear hearing impairment. As a pharmaceutical agent for this purpose, biguanide compounds represented by the following structural formula (I) or a rapamycin derivative represented by the following structural formula (II) as an active ingredient is provided: ##STR00001##
wherein R.sup.1 to R.sup.7 are each independently selected from a hydrogen atom, a halogen atom, or a C.sub.1-6 alkyl group, a C.sub.3-8 cycloalkyl group, a C.sub.6-10 aryl group, a 5- or 6-membered heteroaryl group, or a 5- or 6-membered non-aromatic heterocyclic group, each of which may have a substituent selected from a halogen atom, a cyano group, a C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group, a C.sub.1-6 alkoxy carbonyl group, a C.sub.3-8 cycloalkyl group, a C.sub.2-6 alkenyl group, a C.sub.2-6 alkynyl group, and a phenyl group; ##STR00002##
wherein R.sub.1 is a C.sub.1-6 alkyl or a C.sub.3-6 alkynyl, R.sub.2 is H, —CH2-OH or —CH.sub.2—CH.sub.2—OH, and X is ═O, (H, H) or (H, OH).

The present invention relates to fusion proteins which are capable of binding to phosphatidylserine comprising a phosphatidylserene binding ligand and a modified O6-alkylguanine-DNA alkyltransferase which is capable of autoconjugation to an O6-benzylguanine-modified label, the fusion proteins being capable of binding to phosphatidylserine on the surface of a cell undergoing apoptosis. The invention also relates to recombinant polypeptide precursors of the fusion proteins which comprise a secretion leader sequence, purification tag, protease cleavage site and the fusion protein. Also included in the scope of the invention are nucleic acids encoding the recombinant polypeptide precursor, vectors comprising the nucleic acids, host cells comprising the vectors, methods of production of the fusion proteins, kits and assays for detecting apoptosis.

Described are cell-based cancer vaccines and anti-cancer immunotherapies. The vaccines include isolated tumor cells activated with one or more genotoxic drugs, and, optionally, treated with one or more MK2 inhibitors. The activated cells are highly immunogenic non-proliferative cells, and may be tested for immunogenicity ex vivo for priming T cells by co-incubating the isolated activated cells with dendritic cells and T cells. The vaccines are typically administered into patient's tumor to provide an intratumoral immune activation. Immune checkpoint inhibitor(s) (ICI) may be administered before, during, or after vaccine administration. ICI may be a component of the vaccine. The vaccines confer heightened cytotoxic immune response against the cancer cells, induce tumor regression, and enhance survival from cancer. The vaccines prevent tumor recurrence and induce a long-lasting anti-tumor immunological memory.

A cell composition composed of spermatogonial stem cells, Sertoli cells, Leydig cells and optionally peritubular cells, is provided, as is a culture composition, artificial testicular construct, hydrogel composition, and device containing the same. A method for using the device as a physiologically relevant in vitro model of human testicular function to screen compounds for pharmacological or toxicological activity is also provided.

Disclosed herein are regulators, e.g., inhibitors or promoters, of human pluripotent stem cells (hPSCs), and methods of using the same. Also provided herein are methods of manufacturing hPSCs, and methods of modifying hPSCs comprising contacting the hPSCs with the regulators, e.g., inhibitors or promoters, of hPSCs, and uses thereof.

Disclosed herein are methods for increasing antisense oligonucleotide activity in a cell by modulating autophagy of the cell. In certain embodiments, a compound comprising an antisense oligonucleotide is co-administered to a subject with an autophagy modulator.

The present invention discloses a method of identifying agents that affect human astrocytes functionality using ex-vivo differentiated pluripotent stem cells (PSC). In addition, the use of human progenitor astrocytes or human astrocytes for the treatment of Amyotrophic Lateral Sclerosis (ALS) in a human subject is also disclosed.