Mesenchymal Stem Cell Therapy for Osteoradionecrosis of the Mandible: a Systematic Review of Preclinical and Human Studies

Gundestrup, Anders Kierkegaard; Lynggaard, Charlotte Duch; Forner, Lone; Heino, Terhi J.; Jakobsen, Kathrine Kronberg; Fischer‐Nielsen, Anne; Grønhøj, Christian; Buchwald, Christian von

doi:10.1007/s12015-020-10034-5

Cited by 15 publications

(9 citation statements)

References 43 publications

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“…Mesenchymal stem cells (MSCs) are a type of cell that can selfreplicate and differentiate into bone marrow and other tissues, such as muscle, nervous and connective tissue. 1,2 This has resulted in their wide use to cure many type of diseases. 3 For example, MSCs have been applied in radiation-induced lung injury, 4 renal transplantation, 5 systemic lupus erythematous, 6 even COVID-19, 7 etc.…”

Section: Introductionmentioning

confidence: 99%

Developing electropositive citric acid–polyethylenimine carbon quantum dots with high biocompatibility and labeling performance for mesenchymal stem cells in vitro and in vivo

et al. 2022

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Section: Introductionmentioning

confidence: 99%

Developing electropositive citric acid–polyethylenimine carbon quantum dots with high biocompatibility and labeling performance for mesenchymal stem cells in vitro and in vivo

et al. 2022

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“…Molecularly, MSC-CM strongly increased proliferation of human parotid epithelial cells and decreased irradiation-induced cell death rates in vitro and in vivo [ 46 ]. Furthermore, for other radiotherapy-related injuries in the head-and-neck region, such as mucositis and osteoradionecrosis, both cellular MSC therapies and MSC-CM have been studied [ 14 , 47 ]. We investigated both direct MSC co-culture and indirect MSC-CM co-culture and could not reveal radioprotective effects in any of the two approaches.…”

Section: Discussionmentioning

confidence: 99%

“…Better prognoses result in an increasing need for causative treatments of chronic toxicities in order to improve patients’ long-term quality-of-life. In this context, several preclinical and some clinical studies have shown the potential of stem cell-based therapies for radiotherapy-induced normal tissue toxicities [ 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Human Mesenchymal Stromal Cells Do Not Cause Radioprotection of Head-and-Neck Squamous Cell Carcinoma

Rühle

Lies

Strack

et al. 2022

IJMS

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Radiotherapy of head-and-neck squamous cell carcinoma (HNSCC) can cause considerable normal tissue injuries, and mesenchymal stromal cells (MSCs) have been shown to aid regeneration of irradiation-damaged normal tissues. However, utilization of MSC-based treatments for HNSCC patients undergoing radiotherapy is hampered by concerns regarding potential radioprotective effects. We therefore investigated the influence of MSCs on the radiosensitivity of HNSCCs. Several human papillomavirus (HPV)-negative and HPV-positive HNSCCs were co-cultured with human bone marrow-derived MSCs using two-dimensional and three-dimensional assays. Clonogenic survival, proliferation, and viability of HNSCCs after radiotherapy were assessed depending on MSC co-culture. Flow cytometry analyses were conducted to examine the influence of MSCs on irradiation-induced cell cycle distribution and apoptosis induction in HNSCCs. Immunofluorescence stainings of γH2AX were conducted to determine the levels of residual irradiation-induced DNA double-strand breaks. Levels of connective tissue growth factor (CTGF), a multifunctional pro-tumorigenic cytokine, were analyzed using enzyme-linked immunosorbent assays. Neither direct MSC co-culture nor MSC-conditioned medium exerted radioprotective effects on HNSCCs as determined by clonogenic survival, proliferation, and viability assays. Consistently, three-dimensional microwell arrays revealed no radioprotective effects of MSCs. Irradiation resulted in a G2/M arrest of HNSCCs at 96 h independently of MSC co-culture. HNSCCs’ apoptosis rates were increased by irradiation irrespective of MSCs. Numbers of residual γH2AX foci after irradiation with 2 or 8 Gy were comparable between mono- and co-cultures. MSC mono-cultures and HNSCC-MSC co-cultures exhibited comparable CTGF levels. We did not detect radioprotective effects of human MSCs on HNSCCs. Our results suggest that the usage of MSC-based therapies for radiotherapy-related toxicities in HNSCC patients may be safe in the context of absent radioprotection.

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“…Mesenchymal stem cells could also play an important osteogenesis and bone regeneration role in cases of osteoradionecrosis [79], a severe and difficult-tomanage complication of the jawbone following high-dose radiation therapy in cases of head and neck cancer.…”

Section: Osteonecrosismentioning

confidence: 99%

Gene and Cell Therapy in Dental Tissue Regeneration

Pablo¹,

Serrano²,

García-Arranz³

et al. 2022

Human Tooth and Developmental Dental Defects - Compositional and Genetic Implications

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Advanced therapies hold substantial promise for the treatment of periodontal conditions. Gene therapy has the potential to transfer “therapeutic” genes, which express proteins such as bone morphogenetic proteins, osteoprotegerin, and tissue nonspecific alkaline phosphatase, which is deficient in patients with hypophosphatasia, a condition that affects mineralization of teeth and bone. Transferred genes may also express platelet-derived growth factor, which modulates the growth of periodontal tissue and the alveolar bone. As regards cell therapy, several clinical trials have shown that mesenchymal stem cells, when used with different kinds of scaffolds to enable the required three-dimensional environment, possess a bone regeneration potential that is particularly useful in such disorders as osteoporosis and osteonecrosis, or for regenerating alveolar bone (osseointegration) prior to placing a dental implant. However, much work is still required before these new therapies become true alternatives in routine clinical dental practice. Medical advances require investments, which are usually influenced by the priorities of both politicians and society at large. This will contribute to promoting innovation, efficient treatments, medium- and long-term savings, and a higher quality of life.

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Mesenchymal Stem Cell Therapy for Osteoradionecrosis of the Mandible: a Systematic Review of Preclinical and Human Studies

Cited by 15 publications

References 43 publications

Developing electropositive citric acid–polyethylenimine carbon quantum dots with high biocompatibility and labeling performance for mesenchymal stem cells in vitro and in vivo

Developing electropositive citric acid–polyethylenimine carbon quantum dots with high biocompatibility and labeling performance for mesenchymal stem cells in vitro and in vivo

Human Mesenchymal Stromal Cells Do Not Cause Radioprotection of Head-and-Neck Squamous Cell Carcinoma

Gene and Cell Therapy in Dental Tissue Regeneration

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