The disclosure is directed to compositions and methods comprising genetically engineered fibroblasts for inhibiting progression of a cancerous tumor.

Dosage units consist of an autologous cell therapy product composed of fibroblasts grown for each individual to be treated. The suspension of autologous fibroblasts, grown from a biopsy of each individual's own skin using current good manufacturing practices (CGMP), and standard tissue culture procedures, is supplied in vials containing cryopreserved fibroblasts or precursors thereof, having a purity of at least 98% fibroblasts and a viability of at least 85%, for administration of from one to six mL, preferably two mL, of cells at a concentration of from 1.0-2.0×10.sup.7 cells/mL. When injected into the nasolabial fold wrinkles (creases on the sides of the nose that extend to the corners of the mouth), the autologous fibroblasts are thought to increase the synthesis of extracellular matrix components, including collagen, reducing the severity of these wrinkles. Dosage and timing of administration have been demonstrated to be critical to achieving clinically significant outcomes.

Over the course of an aging process fibroblasts lose contractility, leading to reduced connective tissue stiffness. A promising therapeutic avenue for functional rejuvenation of connective tissue is reprogrammed fibroblast replacements with a laterally confined growth of fibroblasts on micro-patterned substrates that induces stem cell-like spheroids. The partially reprogrammed spheroids are embedded in collagen-I matrices of varying densities, mimicking different 3D tissue constraints. The spheroids regain their fibroblastic properties and sprout to form 3D connective tissue networks. The differentiated fibroblasts exhibit reduced DNA damage, enhanced cytoskeletal gene expression and acto-myosin contractility. The rejuvenated fibroblasts show increased matrix protein (fibronectin and laminin) deposition and collagen remodeling compared to the parental fibroblast tissue network. The partially reprogrammed cells have comparatively open chromatin compaction states and may be more poised to redifferentiation into contractile fibroblasts in 3D-collagen matrix. Collectively, the results highlight efficient fibroblast rejuvenation, with important implications in regenerative medicine.

This invention relates to a tissue construct comprising a core portion having a recess and composed of fibrous connective tissue, and loose fibrous somatic stem cell-accumulated tissue comprising type III collagen and somatic stem cells which is formed in the recess; a device for producing the same; and a method for collecting somatic stem cells from the tissue construct.

A composition comprising cell-derived particles presenting heterologous CD24, wherein the cell is a non-cancerous cell and wherein the composition is substantially devoid of intact cells is disclosed. Methods of producing the cell-derived particles and methods of using the cell-derived particles in treatment of cytokine storm syndrome, tissue injury associated with the inflammation and Coronavirus infection are also disclosed.

The invention relates to in vitro methods for isolating, or producing selected populations of human epicardial cells derived from human pluripotent stem cells; defined mixtures of said cells, and therapeutic uses thereof. Said population comprises epicardial cells with or without the potential to differentiate into cardiac fibroblasts, or a mixture thereof.

Disclosed are a biomimic system simulating lung tissue, a method for manufacturing same, and a microfluidic control method using same, wherein the biomimic system comprises lung epithelial cells and lung fibroblasts, which are isolated from human lungs, and commercially available vascular endothelial cells, and wherein a microfluid flows through the biomimic system. Each chamber inside the corresponding system can allow a fluid, which contains gas and a medium, to flow therethrough and simulate respiration-like movement, wherein all of the three types of cells can survive inside the system even when one week or more have elapsed after through-flow of the fluid. In addition, the pH and pO.sub.2 in the chamber can be monitored by using a pH sensor and a gas partial pressure sensor inside the system, and thus the three types of cells inside the system can be exposed to external environments, drugs, and the like under the same conditions as in the lungs in vivo. Therefore, a wide range of studies including modeling of lung diseases by harmful substances and testing of therapeutic drug efficacy can be conducted, and further, the utilization to in vitro disease modeling, customized medicine prescriptions, and the like can also be made.

The invention relates to a method for manufacturing a bio-ink by additive deposition, which comprises supplying: a first solution including between 5 and 40 wt. % gelatin; a second solution including between 15 and 35.wt. % alginate; a third solution including between 1 and 15 wt. % fibrinogen, and optionally living cells in suspension; and creating a mixture including: around 35 to 65 vol. % of the first solution; around 15 to 35 vol. % of the second solution; and around 15 to 35 vol. % of the third solution, said proportions being selected so that they add up to 100%. Said bio-ink allows the additive deposition of objects that can be polymerised by means of a solution including calcium ions and thrombin. Said objects can be incubated and can be used as a substitute for body tissue, for example (with added fibroblasts) as skin substitute.

A method of obtaining a pluripotent-like multipotent cell, including providing a cell of a first type which is not a pluripotent-like multipotent cell; contacting the cell of a first type with an agent capable of remodeling the chromatin and/or DNA of the cell; transiently increasing expression of at least one pluripotent gene regulator in the cell of a first type, to a level at which the at least one pluripotent gene regulator is capable of driving transformation of the cell of a first type into the pluripotent-like multipotent cell; and placing or maintaining the cell in a differentiation medium and maintaining intracellular levels of the at least one pluripotent gene regulator for a sufficient period of time to allow a stable pluripotent-like multipotent cell to be obtained; wherein the pluripotent-like multipotent cell so obtained does not exhibit teratoma formation in vivo.

Disclosed are methods of promoting wound healing in a patient in need thereof comprising administering to the patient a composition comprising a neonatal fibrin scaffold. Further disclosed are in vitro methods for evaluating a target composition on human wound healing comprising a neonatal porcine plasma scaffold with the target composition and evaluating scaffold properties of the plasma sample.