Novel murine xenograft model for the evaluation of stem cell therapy for profound dysphagia

Kuhn, Maggie A.; Black, Amanda B.; Siddiqui, Mohamed Tausif; Nolta, Jan A.; Belafsky, Peter C.

doi:10.1002/lary.26666

Cited by 5 publications

(6 citation statements)

References 26 publications

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“…19 Kuhn et al later demonstrated survival of human muscle-derived cells injected into the tongue ofimmune-deficient mice post-hemiglossectomy. 13 Animals injected with MDCs weighed significantly more than control animals 12 weeks after treatment, suggesting improved alimentation. Plowman et al examined the effects of autologous muscle-derived stem cells in a denervated ovine tongue model.…”

Section: Discussionmentioning

confidence: 94%

“…[7][8][9][10]18 Several studies have reported the formation of new muscle fibers following the injection of muscle-derived progenitor cells in a rodent hemiglossectomy model. [11][12][13] Kim et al injected a hydrogel-myoblast composite in a rat hemiglossectomy model and observed significant increase in tongue weight, evidence of neovascularization, and possible neurotization. 12 Their results were supported by a study conducted by Bunaprasert et al, who reported that rats receiving myoblast transplantation, whether via gel suspension or in the form of undifferentiated or differentiated constructs, showed superior quality of the muscular regenerate compared to controls.…”

Section: Discussionmentioning

confidence: 99%

“…10 In animal studies, muscle-derived cells have successfully integrated within tissue to improve tongue strength and function. [11][12][13][14] The purpose of this phase I open-label clinical trial was to evaluate the safety and potential efficacy of AMDC for From the Department of Otolaryngology-Head and Neck Surgery (N.N.-Z., M.A.K., L.E., J.D.A., D.G.F., P.C.B. ), University of California, Davis Medical Center, Sacramento, California, U.S.A.; Institute for Regenerative Cures, Department of Internal Medicine (J.A.N.…”

Section: Introductionmentioning

confidence: 99%

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Autologous Muscle‐Derived Cell Therapy for Swallowing Impairment in Patients Following Treatment for Head and Neck Cancer

et al. 2021

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Objectives/Hypothesis: To evaluate the safety and potential efficacy of autologous muscle-derived cells (AMDCs) for the treatment of swallowing impairment following treatment for oropharynx cancer.Study Design: Prospective, phase I, open label, clinical trial. Methods: Oropharynx cancer survivors disease free ≥2 years post chemoradiation were recruited. All patients had swallowing impairment but were not feeding tube dependent (Functional Oral Intake Scale [FOIS] ≥ 5). Muscle tissue (50-250 mg) was harvested from the vastus lateralis and 150 Â 10 6 AMDCs were prepared (Cook MyoSite Inc., Pittsburgh, PA). The cells were injected into four sites throughout the intrinsic tongue musculature. Participants were followed for 24 months. The primary outcome measure was safety. Secondary endpoints included objective measures on swallowing fluoroscopy, oral and pharyngeal pressure, and changes in patient-reported outcomes.Results: Ten individuals were enrolled. 100% (10/10) were male. The mean age of the cohort was 65 (AE8.87) years. No serious adverse event occurred. Mean tongue pressure increased significantly from 26.3 (AE11.1) to 31.8 (AE9.5) kPa (P = .017). The mean penetration-aspiration scale did not significantly change from 5.6 (AE2.1) to 6.8 (AE1.8), and the mean FOIS did not significantly change from 5.4 (AE0.5) to 4.6 (AE0.7). The incidence of pneumonia was 30% (3/10) and only 10% (1/10) experienced deterioration in swallowing function throughout 2 years of follow-up. The mean eating assessment tool (EAT-10) did not significantly change from 24.1 (AE5.57) to 21.3 (AE6.3) (P = .12).Conclusion: Results of this phase I clinical trial demonstrate that injection of 150 Â 10 6 AMDCs into the tongue is safe and may improve tongue strength, which is durable at 2 years. A blinded placebo-controlled trial is warranted.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Autologous Muscle‐Derived Cell Therapy for Swallowing Impairment in Patients Following Treatment for Head and Neck Cancer

et al. 2021

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“… 7 More recently, cell therapy with autologous myoblasts for radiation induced tongue atrophy has been investigated. 6 , 9 In 2022, Schar et al, described a novel surgical treatment which uses hyaluronic acid and lipofilling for pharyngeal tongue base augmentation. 10 They report increased pharyngeal pressure and improved dysphagia symptoms postoperatively.…”

Section: Discussionmentioning

confidence: 99%

Tongue base augmentation to improve swallow function in a cadaveric model

Ramaswamy

Cates

Evangelista

et al. 2023

Laryngoscope Investig Oto

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Objectives To evaluate the feasibility of using Calcium Hydroxylapatite (CaHA) to augment the tongue base for patients with swallowing impairment due to tongue base atrophy. Methods A fresh human cadaver was obtained through the institution's body donation program and baseline lateral fluoroscopic images were obtained. A total of 2 mL of CaHA (Prolaryn Plus) were injected into three sites of the base of tongue under flexible endoscopic guidance with a 22G, 1.5‐inch needle (Monoject, Cardinal Health). Post‐lateral fluoroscopic images were obtained and pharyngeal area (cm 2 ) and tongue base to pharyngeal wall distance (cm) was measured pre‐ and postinjection using SwallowTail fluoroscopic measurement software (Belldev Medical). Results The procedure was easily performed and the CaHA flowed easily into the cadaveric tongue without evidence of extrusion. The pre‐procedural pharyngeal area decreased from 24.36 to 23.14 cm after augmentation. The base of tongue to pharyngeal wall distance decreased from 2.21 to 1.32 cm after augmentation. Conclusion Tongue base augmentation with CaHA may be a feasible adjuvant therapy for the management of swallowing impairment secondary to tongue base atrophy. Further investigation is necessary to evaluate the clinical safety and efficacy. Level of Evidence 4

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“…More recently, human cells have been investigated in immune-deficient rodents, taking a step closer to human translation. Kuhn et al[ 23 ] demonstrated persistence of human MDSCs injections in immune deficient mice. MDSC survival was assessed using in vivo imaging to visualize luciferase-transduced MDSCs.…”

Section: Stem Cell Therapies For Tongue Dysfunctionmentioning

confidence: 99%

Stem cell treatments for oropharyngeal dysphagia: Rationale, benefits, and challenges

Tran¹,

Juarez²,

Long³

2020

WJSC

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Dysphagia, defined as difficulty swallowing, is a common symptom negatively impacting millions of adults annually. Estimated prevalence ranges from 14 to 33 percent in those over age 65 to over 70 percent in a nursing home setting. The elderly, those with neurodegenerative diseases, head and neck cancer patients, and those with autoimmune conditions such as Sjögren's syndrome are disproportionately affected. Oropharyngeal dysphagia refers specifically to difficulty in initiating a swallow due to dysfunction at or above the upper esophageal sphincter, and represents a large proportion of dysphagia cases. Current treatments are limited and are often ineffective. Stem cell therapy is a new and novel advancement that may fill a much-needed role in our treatment regimen. Here, we review the current literature regarding stem cell treatments for oropharyngeal dysphagia. Topics discussed include tissue regeneration advancements as a whole and translation of these principles into research surrounding tongue dysfunction, xerostomia, cricopharyngeal dysfunction, and finally an overview of the challenges and future directions for investigation. Although this field of study remains in its early stages, initial promising results show potential for the use of stem cell-based therapies to treat oropharyngeal dysphagia and warrant further research.

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Novel murine xenograft model for the evaluation of stem cell therapy for profound dysphagia

Cited by 5 publications

References 26 publications

Autologous Muscle‐Derived Cell Therapy for Swallowing Impairment in Patients Following Treatment for Head and Neck Cancer

Autologous Muscle‐Derived Cell Therapy for Swallowing Impairment in Patients Following Treatment for Head and Neck Cancer

Tongue base augmentation to improve swallow function in a cadaveric model

Stem cell treatments for oropharyngeal dysphagia: Rationale, benefits, and challenges

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