Wharton's Jelly for Augmented Cleft Palate Repair in a Rat Critical-Size Alveolar Bone Defect Model

Sahai, Suchit; Wilkerson, Marysuna; Xue, Hasen; Moreno, Nicolas F.; Carrillo, Louis A.; Flores, Rene; Greives, Matthew R.; Olson, Scott D.; Cox, Charles S.; Triolo, Fabio

doi:10.1089/ten.tea.2019.0254

Cited by 9 publications

(3 citation statements)

References 47 publications

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“…However, the primary therapeutic activity of MSCs appears to be paracrine, with secretion of bioactive factors stimulating local survival and recovery of injured cells [5] as well as modulating local inflammation and immune responses [6]. Pre-clinical and clinical research efforts have therefore focused on indications that might be responsive to regenerative MSC bystander effects, including bone defects, such as in cleft palate [7]; tissue ischemia, such as in myocardial infarction [8] or stroke [9]; disorders associated with neuro-inflammation, such as traumatic brain injury [10], cerebral palsy [11] and neonatal stroke [12]; disorders with associated chronic inflammation, such as bronchopulmonary dysplasia [13]; conditions of autoimmune dysregulation, such as lupus erythematosus [14]; and conditions of undesirable immune response, such as graft-versus-host disease [15].…”

Section: Introductionmentioning

confidence: 99%

Comparison of umbilical cord tissue-derived mesenchymal stromal cells isolated from cryopreserved material and extracted by explantation and digestion methods utilizing a split manufacturing model

et al. 2020

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Background aims: Umbilical cord (UC) tissue is recognized as an advantageous source of mesenchymal stromal cells (MSCs), whose therapeutic properties are being actively evaluated in pre-clinical and clinical trials. In recognition of its potential value, storage of UC tissue or cells from UC tissue in newborn stem cell banks is now commonplace; however, strategies for isolating UC-derived MSCs (UCMSCs) from UC tissue have not been standardized. The majority of newborn stem cell banks take one of two approaches to cord tissue processing and cryopreservation: enzymatic digestion of the fresh tissue with cryopreservation of the subsequent cell suspension or cryopreservation of the tissue as a composite whole with later, post-thaw isolation of cells by explantation. Evaluation of UCMSCs derived by these two principal preparation and cryopreservation strategies is important to understanding whether the methods currently employed by newborn stem cell banks retain the desirable clinical attributes of UC cells. Methods: UCMSCs were isolated from 10 UC tissue samples by both explantation and enzymatic digestion methods to allow for comparison of cells from the same donor. Cell isolates from both methods were compared pre-and post-cryopreservation as well as after serial passaging. Cell viability, morphology, growth kinetics, immunophenotype, cytokine secretion and differentiation capacity were evaluated. Results: UCMSCs could be derived from fresh UC tissue by both explantation and digestion methods and from thawed UC tissue by explantation. Initial cell populations isolated by digestion were heterogeneous and took longer to enrich for UCMSCs in culture than populations obtained by explantation. However, once isolated and enriched, UCMSCs obtained by either method showed no significant difference in viability, morphology, rate of proliferation, surface marker expression, levels of cytokine secretion or differentiation capacity. Conclusions: Derivation of UCMSCs by explantation after thawing UC cryopreserved as a composite tissue may be favorable in terms of initial purity and number of cells achievable by a specific passage. However, we observed no evidence of functional difference between UCMSCs derived by explanation or digestion, suggesting that cells isolated from cryopreserved material obtained by either method maintain their therapeutic properties.

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Section: Introductionmentioning

confidence: 99%

Comparison of umbilical cord tissue-derived mesenchymal stromal cells isolated from cryopreserved material and extracted by explantation and digestion methods utilizing a split manufacturing model

et al. 2020

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“…According to studies conducted by Mueller et al 8 and Baba et al 10 , the subcutaneous implantation of UCMSCs with hydroxyapatite scaffold or granules does not led to mature bone formation. In contrast, Sahai et al 11 and Sun et al 12 demonstrated that the combination of UCMSCs with Wharton’s jelly or collagen scaffold has led to favorable outcomes after 6 months. As a result, it can be concluded that UCMSCs have more osteoinductive potential, which consequently makes them ideal for stem cell co-transplantation in cases in which other sources of stems cell are not sufficient, such as stem cells from human exfoliated deciduous teeth (SHED), dental pulp stem cells (DPSCs), muscle-derived stem cells (MDSCs), and adipose-derived stem cells (ADSCs), especially in children who have a smaller number of cells for cleft regeneration.…”

Section: Stem Cell Therapymentioning

confidence: 95%

Use of stem cells in bone regeneration in cleft palate patients: review and recommendations

Amiri

Lavaee

Danesteh

2022

JKAOMS

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This study was conducted to review the efficacy of different sources of stem cells in bone regeneration of cleft palate patients. The majority of previous studies focused on the transplantation of bone marrow mesenchymal stem cells. However, other sources of stem cells have also gained considerable attention, and dental stem cells have shown especially favorable outcomes. Additionally, approaches that apply the co-culture and co-transplantation of stem cells have shown promising results. The use of different types of stem cells, based on their accessibility and efficacy in bone regeneration, is a promising method in cleft palate bone regeneration. In this regard, dental stem cells may be an ideal choice due to their efficacy and accessibility. In conclusion, stem cells, despite the lengthy procedures required for culture and preparation, are a suitable alternative to conventional bone grafting techniques.

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“…[6][7][8] Preliminary animal model investigation in rats has demonstrated that implantation of human Wharton jelly, which contains mesenchymal stem cells (MSCs), can lead to bone regeneration in critical-sized alveolar bone defects. 9 Both UC blood and tissue contain h-UCMSCs, which can be harnessed in regenerative medicine because of their capacity for self-renewal, multipotent differentiation, and enhanced proliferative capacity. 6 Using newborn tissue as a stem cell source is advantageous because UC blood and tissue are usually disposed of as medical waste after the delivery of the neonate, which makes collection straightforward and noninvasive.…”

mentioning

confidence: 99%

A Murine Calvarial Defect Model for the Investigation of the Osteogenic Potential of Newborn Umbilical Cord Mesenchymal Stem Cells in Bone Regeneration

Stanton

Feng

Kondra

et al. 2023

Plastic &Amp; Reconstructive Surgery

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left lip and/or palate (CLP), is the most common craniofacial congenital disability, affecting an estimated one in 700 live births. 1,2 Most patients with complete CLP also have an alveolar cleft. The mainstay of alveolar cleft repair (ACR) at many institutions is secondary alveolar bone grafting (ABG), with autogenous iliac crest bone graft (ICBG) being the standard graft material. However, this procedure is associated with significant donor-site morbidity, including hematoma, pain, and disfiguring scars. 3Background: The standard graft material for alveolar cleft repair (ACR) is autogenous iliac crest. A promising alternative potential graft adjunct-newborn human umbilical cord mesenchymal stem cells (h-UCMSCs)-has yet to be explored in vivo. Their capacity for self-renewal, multipotent differentiation, and proliferation allows h-UCMSCs to be harnessed for regenerative medicine. This study sought to evaluate the efficacy of using tissue-derived h-UCMSCs and their osteogenic capabilities to improve ACR in a murine model. Methods: Foxn1 mice were separated into three groups with the following calvarial defects: no treatment (empty defect; n = 6), poly(D,L-lactide-co-glycolide) (PLGA) scaffold (n = 6), or h-UCMSCs with PLGA (n = 4). Bilateral 2-mmdiameter parietal bone critical-sized defects were created using a dental drill. Microcomputed tomography (microCT) imaging was performed 1, 2, 3, and 4 weeks postoperatively. The mice were euthanized 4 weeks postoperatively for RNAScope, immunohistochemical, and histological analysis. Results: No mice experienced complications during the follow-up period. MicroCT imaging and histological analysis demonstrated that the no-treatment and PLGA-only defects remained patent without significant defect size differences across groups. In contrast, the h-UCMSCs with PLGA group had significantly greater bone fill on microCT and histological analysis. Conclusions: This study demonstrates a successful calvarial defect model for the investigation of h-UCMSC-mediated osteogenesis and bone repair. Evidence reveals that PLGA alone has neither short-term effects on bone formation nor any unwanted side effects, making it an attractive scaffold. Further investigation using h-UCMSCs with PLGA in larger animals is warranted to advance future translation to patients requiring ACR.

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Wharton's Jelly for Augmented Cleft Palate Repair in a Rat Critical-Size Alveolar Bone Defect Model

Cited by 9 publications

References 47 publications

Comparison of umbilical cord tissue-derived mesenchymal stromal cells isolated from cryopreserved material and extracted by explantation and digestion methods utilizing a split manufacturing model

Comparison of umbilical cord tissue-derived mesenchymal stromal cells isolated from cryopreserved material and extracted by explantation and digestion methods utilizing a split manufacturing model

Use of stem cells in bone regeneration in cleft palate patients: review and recommendations

A Murine Calvarial Defect Model for the Investigation of the Osteogenic Potential of Newborn Umbilical Cord Mesenchymal Stem Cells in Bone Regeneration

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