Porcine small intestine submucosal grafts improve remucosalization and progenitor cell recruitment to sites of upper airway tissue remodeling

Nayak, Jayakar V.; Rathor, Aakanksha; Grayson, Jessica W.; Bravo, Dawn T.; Velasquez, Nathalia; Noel, Julia E.; Beswick, Daniel M.; Riley, Kristen; Patel, Zara M.; Cho, Do‐Yeon; Dodd, Robert; Thamboo, Andrew; Choby, Garret; Walgama, Evan; Harsh, Griffith R.; Hwang, Peter H.; Clemons, Lisa; Lowman, Deborah; Richman, Joshua S.; Woodworth, Bradford A.

doi:10.1002/alr.22156

Cited by 24 publications

(21 citation statements)

References 42 publications

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“…30 When used to cover exposed cartilage or bone after elevation of nasoseptal flaps in anterior skull base reconstructions, SISG use results are faster in remucosolization and healing as compared with autologous grafts. 31 While safe and effective SISG use becomes increasingly common in various otolaryngology procedures, SISG use in lateral skull base reconstruction has yet to be examined.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Small Intestinal Submucosal Graft and Autologous Tissue in Prevention of CSF leak after Posterior Fossa Craniotomy

Totten

Manzoor

Yancey

et al. 2021

J Neurol Surg B Skull Base

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Objective To compare the use of porcine small intestinal submucosal grafts (SISG) and standard autologous material (fascia) in prevention of cerebrospinal fluid (CSF) leak and pseudomeningocele formation after translabyrinthine resection. Setting Set at the tertiary skull base center. Methods This is a retrospective chart review. After Institutional Review Board approval, we performed a retrospective cohort study evaluating CSF leak in patients who underwent resection of lateral skull base defects with multilayered reconstruction using either fascia autograft or porcine SISGs. Demographics were summarized with descriptive statistics. Logistic regression was used to compare autograft and xenograft cohorts in terms of CSF complications. Results Seventy-seven patients underwent lateral skull base resection, followed by reconstruction of the posterior cranial fossa. Of these patients, 21 (27.3%) underwent multilayer repair using SISG xenograft. There were no significant differences in leak-associated complications between autograft and xenograft cohorts. Ventriculoperitoneal shunt was necessary in one (1.8%) autograft and one (4.8) xenograft cases (p = 0.49). Operative repair to revise surgical defect was necessary in three (5.4%) autograft cases and none in xenograft cases. Conclusion The use of SISG as a component of complex skull base reconstruction after translabyrinthine tumor resection may help reduce CSF leak rates and need for further intervention.

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Section: Discussionmentioning

confidence: 99%

Comparison of Small Intestinal Submucosal Graft and Autologous Tissue in Prevention of CSF leak after Posterior Fossa Craniotomy

Totten

Manzoor

Yancey

et al. 2021

J Neurol Surg B Skull Base

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“…Meanwhile, though not specifically studied in this population, enhanced donor‐site recovery could potentially influence the rates of postoperative deformities if indeed flap harvest was the underlying etiology. There is increasing evidence that donor site reconstruction with a free mucosal graft or xenoplastic graft is associated with faster rates to postoperative septal remucosalization.…”

Section: Discussionmentioning

confidence: 99%

Prospective characterization of postoperative nasal deformities in patients undergoing endoscopic endonasal skull‐base surgery

Rowan

Valappil

Chen

et al. 2019

Int Forum Allergy Rhinol

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Background Surgeons have become increasingly aware of the impact of endoscopic endonasal surgery (EES) of the skull base on sinonasal‐related quality of life. Prior retrospective investigation described a correlation between nasoseptal flap (NSF) reconstruction in EES with postoperative nasal deformities, such as nasal dorsum collapse. The primary objective of this study was to prospectively evaluate the incidence of, and contributing factors to, postoperative changes in nasal structure following EES. Secondary goals included assessing subjective changes in nasal appearance as well as objective nasal analysis. Methods Clinical demographics and detailed perioperative information was prospectively collected for patients undergoing transsellar/suprasellar EES for skull‐base tumors. Preoperatively, 1‐month and 6‐month photographs were completed for objective photographic nasal analysis and blinded assessment by surgeons. Subjective patient feedback was also solicited. Results Overall, 14.7% (5/34) of patients subjectively reported postoperative nasal deformities, whereas both blinded‐surgeon and objective nasal measurements identified deformities in 12.9% (4/31) of patients. Patients with postoperative deformities were more likely to have skull‐base reconstruction with an NSF (p = 0.01) and trended toward an increased incidence in patients with nonpituitary neoplasms (p = 0.07). There were no other associations between clinical or operative characteristics and external deformities. No patients planned to undergo corrective repair. Conclusion External nasal deformities following EES are more frequent than previously acknowledged. Postoperative deformities appear to be associated with NSF reconstruction and may be associated with surgery for nonpituitary neoplasms. Patients should be counseled on this potential outcome, and future studies should investigate how to minimize postoperative sequela.

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“…As a path to transplanting ex vivo genetically corrected autologous cells into patients, we explored whether we could embed genetically edited airway cells on a pSIS membrane that is already in clinical use and FDA approved for several indications, including sinonasal repair (Nayak et al, 2018). We optimized the seeding density and culture conditions to obtain a monolayer of basal cells that retained expression of KRT5.…”

Section: Gene Edited Basal Cells Can Be Embedded In Fda-approved Porcmentioning

confidence: 99%

“…3. Gene edited KRT5+ UABCs were successfully embedded on a FDA-approved porcine small intestinal submucosal (pSIS) surgical matrix routinely used for epithelial repair during functional endoscopic sinus and skull base surgeries (FESS) (Nayak et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Highly Efficient Repair of the ΔF508 Mutation in Airway Stem Cells of Cystic Fibrosis Patients with Functional Rescue of the Differentiated Epithelia

Vaidyanathan

et al. 2019

Preprint

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Cystic fibrosis (CF) is a monogenic autosomal recessive disorder caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Clchannel. CF results in multiorgan dysfunction and ultimately mortality from respiratory sequelae. Although pharmacologic approaches have demonstrated efficacy in reducing symptoms and respiratory decline, a curative treatment modality remains elusive. Gene therapy, a promising curative strategy, has been limited due to poor correction efficiencies both in vitro and in vivo. Here, we use Cas9 and adeno-associated virus 6 (AAV6) to correct the F508 mutation (found in ~70% of CF alleles and ~90% of CF patients in North America) in upper airway basal stem cells (UABCs) obtained from CF and non-CF patients undergoing functional endoscopic sinus surgery (FESS). In UABCs from homozygous (F508/F508) and compound heterozygous (F508/Other) CF patients, we achieved 28  5 % and 42  15% correction, respectively. In homozygous human bronchial epithelial cells (HBECs), we achieved 41 4 % correction. Upon differentiation in air-liquid interface (ALI), cultures of corrected CF cells displayed partial restoration of CFTRinh-172 sensitive Clcurrents relative to non-CF controls: 31 5 % in UABCs and 51  3 % in HBECs (both from subjects homozygous for F508 CFTR). Finally, gene edited cells embedded successfully and retained expression of cytokeratin 5 (KRT5), a basal cell marker, on a FDA-approved porcine small intestinal submucosal (pSIS) membrane previously shown to improve re-mucosalization after FESS. In summary, we present an efficient, feederfree, selection-free and clinically compatible approach to generate cell-based therapies for CF from autologous airway stem cells. This approach represents a first step towards developing patient-specific autologous airway stem cell transplant as a curative treatment for CF.

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Porcine small intestine submucosal grafts improve remucosalization and progenitor cell recruitment to sites of upper airway tissue remodeling

Abstract: This prospective, randomized, controlled trial indicates that a porcine SIS graft placed on exposed cartilage and bone within the upper airway confers improved remucosalization compared to current practice standards.

Cited by 24 publications

References 42 publications

Comparison of Small Intestinal Submucosal Graft and Autologous Tissue in Prevention of CSF leak after Posterior Fossa Craniotomy

Comparison of Small Intestinal Submucosal Graft and Autologous Tissue in Prevention of CSF leak after Posterior Fossa Craniotomy

Prospective characterization of postoperative nasal deformities in patients undergoing endoscopic endonasal skull‐base surgery

Highly Efficient Repair of the ΔF508 Mutation in Airway Stem Cells of Cystic Fibrosis Patients with Functional Rescue of the Differentiated Epithelia

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