Postnatal stem cells and uses thereof
Inventors
Shi, Songtao • Robey, Pamela Gehron • Gronthos, Stan • Miura, Masako
Assignees
US Department of Health and Human Services
Publication Number
US-9175264-B2
Publication Date
2015-11-03
Expiration Date
2023-04-19
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Abstract
The invention generally relates to postnatal dental stem cells and methods for their use. More specifically, the invention relates in one aspect to postnatal dental pulp stem cells, use of the cells to generate dentin, and differentiation of the cells. In another aspect, the invention relates to human postnatal deciduous dental pulp multipotent stem cells, use of the cells to generate dentin, and differentiation of the cells.
Core Innovation
The invention relates generally to postnatal dental stem cells and methods for their use. In particular, it concerns postnatal dental pulp stem cells capable of generating dentin and differentiating into multiple cell types. More specifically, it includes human postnatal deciduous dental pulp multipotent stem cells, their ability to generate dentin, and methods for their differentiation.
The problem addressed by the invention arises from the need for new sources of stem cells and methods for their use in medicine and dentistry. Postnatal stem cells, which can extensively renew themselves and differentiate into specialized cells, are promising for treating diseases and repairing tissue damaged by wear, injury, or disease. However, suitable sources and effective applications of postnatal stem cells, especially for dental applications, were lacking.
The invention provides isolated human postnatal deciduous dental pulp multipotent stem cells (including those from exfoliated deciduous teeth – SHED) that can differentiate into neural cells, adipocytes, and odontoblasts. These cells can be cultured in various media, stored for later use, and induced to generate specific tissues such as bone, neural tissue, adipose tissue, and dentin. The invention also discloses methods to implant these cells into organisms (preferably humans) to promote regeneration of these tissues, including generating reparative dentin on pre-existing dentin surfaces.
Claims Coverage
The patent includes multiple independent claims focusing on isolated postnatal deciduous dental pulp multipotent stem cells, their properties, and compositions containing them. There are three main inventive features identified in these claims.
Isolated clonal population of human postnatal deciduous dental pulp multipotent stem cells
An isolated clonal population of human postnatal deciduous dental pulp multipotent stem cells derived from postnatal deciduous teeth. The cells are capable of differentiating into neural cells, adipocytes, or odontoblasts, can proliferate to over 140 population doublings, are expanded ex vivo, and express the marker CD146.
Composition with biocompatible carrier and stem cells inducing bone formation in vivo
A composition comprising a carrier (such as hydroxyapatite/tricalcium phosphate ceramics, gelatin, polyvinyl sponge, or collagen matrix) combined with a mixed or clonal population of human postnatal deciduous dental pulp multipotent stem cells that induce bone formation when transplanted in vivo and can proliferate extensively. The cells express CD146 and may or may not express STRO-1.
Stem cell characteristics and uses in transplantation
Human postnatal deciduous dental pulp multipotent stem cells within the isolated or clonal populations express specific markers such as STRO-1 and CD146, can generate dentin when transplanted in vivo, induce bone formation without forming bone themselves, and survive as transfected cells expressing exogenous nucleic acid products such as growth factors, cytokines, or chemokines. Clonal cells express neural markers when transplanted into the dentate hippocampus of immunocompromised mice.
The independent claims cover isolated clonal populations of multipotent stem cells from postnatal deciduous teeth characterized by high proliferative capacity and specific marker expression, compositions combining such cells with carriers for therapeutic transplantation to induce bone and dentin formation, and methods involving differentiation and implantation to produce neural cells or express heterologous products.
Stated Advantages
The invention enables restorative generation of dentin within a tooth, avoiding artificial material interfaces that can cause infection and pain.
It provides a novel and highly proliferative source of multipotent postnatal stem cells capable of differentiating into multiple tissue types including neural, adipose, and odontoblast cells.
Methods disclosed facilitate treatment of trauma, degenerative diseases, and dental procedures like root canals by biological tissue regeneration rather than artificial substitutes.
Multipotent dental pulp stem cells can be stored and later used for autologous transplantation, reducing immune rejection risks and improving patient-specific treatment.
Documented Applications
Generating dentin in vivo on pre-existing dentin surfaces such as those present in teeth.
Implantation of stem cells to promote bone formation in sites of physical injury, dental or medical surgery, or degenerative disease such as osteoporosis.
Production of neural tissue within an organism for treatment of neural injury or degenerative diseases including Parkinson's disease and Alzheimer's disease.
Generation of adipose tissue within an organism to treat disorders characterized by deficient fat tissue (lipodystrophies).
Use of dental stem cells implanted into root canal voids to promote reparative dentin formation and improve outcomes of dental treatments.
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