Multipotent postnatal stem cells from human periodontal ligament and uses thereof

Inventors

Shi, SongtaoSeo, Byoung-MooMiura, Masako

Assignees

US Department of Health and Human Services

Publication Number

US-10046012-B2

Publication Date

2018-08-14

Expiration Date

2024-11-22

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Abstract

The invention generally relates to postnatal periodontal ligament stem cells and methods for their use. More specifically, the invention relates in one aspect to postnatal periodontal ligament multipotent stem cells, use of the cells to generate periodontium, differentiation of the cells and methods of tissue cryopreservation.

Core Innovation

The invention relates to isolated human postnatal periodontal ligament multipotent stem cells (PDLSCs) and their use. These PDLSCs can differentiate into multiple cell types including collagen fiber forming cells (fibroblasts), cementoblasts, cementocytes, and adipocytes. The cells can be expanded in tissue culture and implanted into a subject, preferably a human, to generate periodontal tissue such as cementum and periodontal ligament both in vivo and in vitro.

The invention addresses the need for more predictable and effective methods to treat periodontal diseases, which are characterized by destruction of the periodontium including periodontal ligament, cementum, alveolar bone, and gingiva. Existing treatments like guided tissue regeneration and growth factors lack consistent outcomes. The discovery of PDLSCs provides a novel cell-based approach to regenerate lost periodontal tissue, potentially improving treatment for trauma and periodontal disease.

Claims Coverage

The patent includes 2 main independent claims focusing on methods of treating trauma of periodontal tissue using isolated clonal populations of human periodontal ligament multipotent stem cells, including cryopreserved populations.

Use of isolated clonal populations of periodontal ligament multipotent stem cells for treating periodontal tissue trauma

A method of treating periodontal tissue trauma in a subject by locally administering an effective amount of composition containing isolated clonal human multipotent stem cells derived from periodontal ligament. These cells proliferate, express STRO-1 and MUC 18, form colonies in vitro, differentiate into periodontal ligament cells producing collagen fibers and cementum in vivo, and are expanded ex vivo prior to administration.

Use of cryopreserved isolated clonal periodontal ligament multipotent stem cells for treating periodontal tissue trauma

A method comprising thawing a cryopreserved composition containing isolated clonal human multipotent periodontal ligament stem cells, optionally expanding them ex vivo, and administering them locally to the periodontal tissue to treat trauma. These cells share the same characteristics as described above, including marker expression and differentiation potential.

The claims cover methods for periodontal tissue repair involving administration of isolated human postnatal periodontal ligament multipotent stem cells, including methods using cryopreserved cells expanded ex vivo, emphasizing their multipotency, marker expression, clonogenic nature, and in vivo differentiation capacity to regenerate periodontal tissue.

Stated Advantages

The invention provides a novel and predictable method to regenerate lost periodontal tissues, improving treatment of periodontal disease and trauma.

Use of PDLSCs enables minimally invasive placement to produce regenerative periodontal tissue, potentially reducing pain and cost compared to current surgical methods.

Cryopreservation methods allow long-term storage and later recovery of functional periodontal stem cells, facilitating clinical applications and tissue banking.

Documented Applications

Regeneration of periodontal tissues, including cementum and periodontal ligament, for treatment of periodontal disease and trauma resulting from physical injury or dental procedures.

Generation of adipose tissue in vivo by implanting PDLSCs induced to differentiate into adipocytes, useful for conditions with fat deficiency.

Cryopreservation of periodontal ligament tissue to preserve stem cells for later isolation and clinical use in periodontal tissue regeneration.

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