Light as a replacement for mitogenic factors on progenitor cells
Inventors
Romanczyk, Tara B. • Anders, Juanita J. • Waynant, Ronald R. • Ilev, Ilko K. • Longo, Leonardo
Assignees
United States, Health And Services, Secretary of, Department of • National Institutes of Health NIH • Henry M Jackson Foundation for Advancedment of Military Medicine Inc • US Department of Health and Human Services
Publication Number
US-9205276-B2
Publication Date
2015-12-08
Expiration Date
2026-03-30
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Abstract
The present invention generally relates to a method of using light treatment supporting specific cell types in a subject. Specifically, the present invention relates to methods for stimulating the proliferation, migration, differentiation and survival of cell using specific parameter of lights. These methods are particularly useful in the cellular regeneration and replacement in a tissue injury, such as CNS or PNS injury, and in transplantation of organs, tissues and cells.
Core Innovation
The invention relates to methods of using light treatment as a replacement for mitogenic factors to stimulate proliferation, migration, differentiation, and survival of cells, particularly stem and progenitor cells. Through the application of light with specific parameters such as wavelength, power density, and dosage, the methods support cellular regeneration and replacement, especially in tissue injuries like CNS or PNS injuries, neurodegenerative diseases, and contexts involving transplantation of organs, tissues, and cells.
Mitogenic factors traditionally govern the fate and maintenance of cells but are costly and require complex application. The invention addresses the problem of needing these expensive mitogenic growth factors by employing light as a non-invasive substitute able to elicit similar biological effects, including cellular proliferation and differentiation. Light therapy, proven to impact neuronal survival and regeneration through photoreceptors, was not previously used to replace mitogenic factors in supporting cell survivability, proliferation, differentiation, and migration.
The methods comprise exposing stem or progenitor cells, such as neural progenitor cells and various mesenchymal and embryonic stem cells, to light with wavelengths ranging from ultraviolet through infrared, with defined power densities and dosages that promote these cellular processes. The light treatment can be performed in vitro or in vivo and includes specific preferred parameters such as light of about 810 nm wavelength and power densities around 1, 50, or 100 mW/cm2 with defined energy dosages. The light-treated cells, tissues, or organs can be used directly in clinical transplantation or therapeutic interventions, effectively substituting the conventional mitogenic factors.
Claims Coverage
The patent includes eleven independent inventive features mainly related to methods of stimulating cellular differentiation and treating diseases using light-stimulated progenitor cells and defining optimal parameters of light treatment applied ex vivo or in vivo.
Method for providing differentiated cells by ex vivo light exposure and transplantation
Exposing neural progenitor cells ex vivo to laser light in the wavelength range 200-1500 nm at power densities 0.001-500 mW/cm2 results in neuronal differentiation of the cells that are subsequently transplanted into a subject.
Method of culturing light stimulated cells before transplantation
Culturing light-stimulated cells in vitro under conditions that promote cell differentiation prior to transplantation.
Method with specific laser wavelength and power density ranges
Using a laser light source with wavelength range 400-1200 nm and power density 0.5-150 mW/cm2 to stimulate cells.
Method with refined wavelength and power density parameters
Applying laser light with wavelength about 750-1000 nm and power density 0.1-200 mW/cm2 for effective stimulation.
Method with specific preferred wavelength and power densities
Using laser light at about 810 nm wavelength applied at about 1 mW/cm2, 50 mW/cm2, or 100 mW/cm2 power densities to stimulate progenitor cells.
Method for treatment of CNS or PNS injury in subject using light stimulated cells
Treating a subject having central or peripheral nervous system injury by transplanting ex vivo light-stimulated neural progenitor cells differentiated using laser light of defined wavelength and power density.
Method specifying treatment of specific CNS or PNS injuries
Application of the method for injuries like spinal cord injury, stroke, or traumatic brain injury using light-stimulated cells.
Method for treating neurodegenerative diseases using light stimulated cells
Treatment of neurodegenerative diseases including Parkinson's, Alzheimer's, Huntington's, Multiple Sclerosis, and ALS using transplantation of light stimulated progenitor cells.
Method for treating mammalian subjects
Application of light-stimulated cell transplantation methods specifically in mammalian subjects.
Treatment method using ex vivo light stimulation and transplantation for CNS/PNS injury
Ex vivo exposure of human neural progenitor cells to laser light within 200-1500 nm and 0.001-500 mW/cm2 power density followed by transplantation to treat CNS and PNS injury.
Culturing human neural progenitor cells prior to transplantation
Culturing light stimulated human neural progenitor cells to promote their differentiation or proliferation before transplantation into subjects with CNS or PNS injury.
Collectively, the inventive features focus on methods of using specific light parameters ex vivo or in vivo to stimulate neuronal differentiation and proliferation of progenitor cells, and applying these cells therapeutically for nervous system injuries and neurodegenerative diseases through transplantation.
Stated Advantages
Light treatment eliminates or replaces the need for expensive growth factors in cell preparation.
Specific wavelengths of light induce endogenous production of growth factors, facilitating regeneration and cellular replacement in tissue injuries.
Light at specific wavelengths can direct pluripotent cells to differentiate into specific cell types, enhancing regeneration and transplantation outcomes.
Documented Applications
Cellular regeneration and replacement in tissue injuries such as central nervous system (CNS) or peripheral nervous system (PNS) injuries.
Treatment of neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease, Multiple Sclerosis, and ALS.
Use in transplantation of organs, tissues, and cells, including liver transplant, diabetes treatment, and heart diseases like acute myocardial infarction.
In vitro cell culture methods for stimulating proliferation, differentiation, and migration of stem and progenitor cells.
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