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Patch grafting of organoids of stem/progenitors into solid organs can correct genetic-based disease states.

ABSTRACT: Patch grafting, a novel strategy for transplantation of stem/progenitor organoids into porcine livers, has been found successful also for organoid transplantation into other normal or diseased solid organs in pigs and mice. Each organoid contained ∼100 cells comprised of biliary tree stem cells (BTSCs), co-hepato/pancreatic stem/progenitors, and partnered with early lineage stage mesenchymal cells (ELSMCs), angioblasts and precursors to endothelia and stellate cells. Patch grafting enabled transplantation into livers or pancreases of ≥10^8th (pigs) or ≥10^6th-7th (mice) organoids/patch. Graft conditions fostered expression of multiple matrix-metalloproteinases (MMPs), especially secretory isoforms, resulting in transient loss of the organ's matrix-dictated histological features, including organ capsules, and correlated with rapid integration within a week of organoids throughout the organs and without emboli or ectopic cell distribution. Secondarily, within another week, there was clearance of graft biomaterials, followed by muted expression of MMPs, restoration of matrix-dictated histology, and maturation of donor cells to functional adult fates. The ability of patch grafts of organoids to rescue hosts from genetic-based disease states was demonstrated with grafts of BTSC/ELSMC organoids on livers, able to rescue NRG/FAH-KO mice from type I tyrosinemia, a disease caused by absence of fumaryl acetoacetate hydrolase. With the same grafts, if on pancreas, they were able to rescue NRG/Akita mice from type I diabetes, caused by a mutation in the insulin 2 gene. The potential of patch grafting for cell therapies for solid organs now requires translational studies to enable its adaptation and uses for clinical programs.

SUBMITTER: Zhang W

PROVIDER: S-EPMC10495116 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Patch grafting of organoids of stem/progenitors into solid organs can correct genetic-based disease states.

Zhang Wencheng W Wauthier Eliane E Lanzoni Giacomo G Hani Homayoun H Yi Xianwen X Overi Diletta D Shi Lei L Simpson Sean S Allen Amanda A Suitt Carolyn C Ezzell Jennifer Ashley JA Alvaro Domenico D Cardinale Vincenzo V Gaudio Eugenio E Carpino Guido G Prestwich Glenn G Dominguez-Bendala Juan J Gerber David D Mathews Kyle K Piedrahita Jorge J Adin Christopher C Sethupathy Praveen P He Zhiying Z Reid Lola M LM

Biomaterials 20220807

Patch grafting, a novel strategy for transplantation of stem/progenitor organoids into porcine livers, has been found successful also for organoid transplantation into other normal or diseased solid organs in pigs and mice. Each organoid contained ∼100 cells comprised of biliary tree stem cells (BTSCs), co-hepato/pancreatic stem/progenitors, and partnered with early lineage stage mesenchymal cells (ELSMCs), angioblasts and precursors to endothelia and stellate cells. Patch grafting enabled trans ...[more]

PMID: 36030102

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Project description:ImprotanceCorrection of caudal septal deviation with a batten graft has been popularized recently. However, few reports have documented the surgical outcomes of this technique, especially the use of bony batten grafts in septoplasty.ObjectiveTo evaluate the surgical outcomes of bony batten grafting for the management of caudal septal deviation in endonasal septoplasty.Design, setting, and participantsThis retrospective cohort study evaluates the medical records of 141 patients with caudal septal deviation who underwent septoplasty using bony batten grafts from September 1, 2011, through February 29, 2016, at a tertiary referral hospital. Patients were divided into primary and secondary surgery groups. Patients were also divided into the septoplasty plus turbinate surgery and the septoplasty only group. Endoscopic assessment of deviation correction was performed, and postoperative complications were analyzed.Main outcomes and measuresPatient satisfaction and symptom improvement were evaluated via telephone interviews by using the Nasal Obstruction Symptoms Evaluation (NOSE) scores.ResultsOf the 141 patients (24 women [17%] and 117 men [83%]; mean [SD] age, 32.8 [12.9] years), 86 (61%) rated their symptoms in the postoperative survey as much improved; 50 (35.5%), improved; 4 (2.8%), no change; and 1 (0.7%), worse. All patients had significantly improved mean (SD) postoperative NOSE scores (28.7 [22.0]; 95% CI, 25.0-32.4) compared with preoperative scores (70.5 [26.7]; 95% CI, 66.0-75.0; P < .001). No significant intergroup differences were observed in surgical outcome between the 116 patients undergoing primary surgery (mean [SD] NOSE score, 28.2 [21.9]) and 25 undergoing secondary surgery (mean [SD] NOSE score, 30.8 [24.3]; P = .34). No significant difference in surgical outcome was found between the 102 patients in the turbinate surgery group (mean [SD] NOSE score, 28.1 [20.8]) and 39 in the septoplasty only group (mean [SD] NOSE score, 30.4 [23.7]; P = .65). On endoscopic examination for surgical outcome, 128 patients (90.8%) had a straight septum and 13 (9.2%) had improved but residual caudal deviation. Postoperative complications included septal hematoma in 4 patients, hyposmia in 2, and chondritis in 1; all patients were treated successfully. Four patients required revision surgery because of incomplete functional correction or a desire for rhinoplasty.Conclusions and relevanceSeptoplasty using bony batten grafts is useful for correcting caudal septal deviation with favorable surgical outcomes and an acceptable complication rate.Level of evidence3.

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Patch grafting of organoids of stem/progenitors into solid organs can correct genetic-based disease states.

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Patch grafting of organoids of stem/progenitors into solid organs can correct genetic-based disease states.

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