Wang Lab

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Organoid

Organoid research in Wang Lab focuses on tissue engineering and regenerative medicine using organoids. As PI or co-Investigator on several universities- and foundation-funded grants, Dr. Wang laid the groundwork for the proposed research by developing collagen I based gels for the culture of primary intestinal stem cells and use synthetic foam materials as cell carriers for the delivery of intestinal organoids [1, 2], and by demonstrating the feasibility to encapsulate DNA-functionalized gold nanoparticles [3] and drug-loaded PLGA nanoparticles into primary isolated intestinal organoids to form an intestinal Trojan horse for gene regulation therapy of inflammatory bowel disease [4, 5]. Dr. Wang demonstrated that the external perturbations in the lumen, like engineered nanomaterials [6, 7] and dietary interventions [8, 9] controlled the proliferation and differentiation of intestinal organoids ex vivo. Most interestingly, the miniguts treated with 200 ng/ml RANKL for 3 days were immunostained with two M-cells specific marker: GP2 (green) and UEA-1(red), which confirmed the successful inducing of intestinal organoids into M-cells [10]. He further confirmed that the intestinal organoids from different microbiota environment demonstrated the concentration-dependent responses when they are exposed to inflammatory stimulants [11]. Dr. Wang with colleagues have cultured canine intestinal organoids from dogs’ different gut regions, either healthy or diseased [12]. He also used intestinal organoid as a new platform to study alginate and chitosan mediated PLGA nanoparticles for drug delivery [13]. In this study, the impact of surface charge on the delivery of 5-ASA loaded PLGA nanoparticles into the lumen of organoids was investigated. It was concluded that the positively charged nanoparticles were more readily transported across the epithelium into the lumen. Dr. Wang is aware the current major non-genetic cell engineering strategies for drug delivery and cell-based therapies [14-16].

The morphology of intestinal stem cells cultured in Matrigel during 7 days. The scale bars were 200 μm [2].

The morphology of an intestinal organoid cultured in Matrigel during 7 days. The scale bars were 200 μm [Ref. 3].

1) Peng H, Poovaiah N, Forrester M, Cochran E, Wang Q. Ex vivo culture of primary intestinal stem cells in collagen gels and foams. ACS Biomaterials Science & Engineering. 2015; 1(1):37-42. PMID: 33435081.

2) Asama M, Hall A, Qi Y, Moreau B, Walthier H, Schaschwary M, Bristow B, Wang Q. Alternative foaming agents for topical treatment of ulcerative colitis. J Biomed Mater Res A. 2018;106(5):1448-1456. PMID: 29314587.
3) Peng H, Wang C, Xu X, Yu C, Wang Q. An intestinal Trojan horse for gene delivery. Nanoscale. 2015; 7(10):4291-305. PMID: 25619169

4) Davoudi Z, Peroutka-Bigus N, Bellaire B, Wannemuehler M, Barrett TA, Narasimhan B, Wang Q. Intestinal Organoids Containing PLGA Nanoparticles for the Treatment of Inflammatory Bowel Diseases. Journal of biomedical materials research. Part A. 2018; 106(4): 876-886. PMID: 29226615

5) Davoudi Z, Qi Y, Wang Q. Colonic Stem Cells Mediated Drug Delivery to Treat Ulcerative Colitis. Nanomedicine: Nanotechnology, Biology and Medicine. 2018; 14(5):1750.

6) Qi Y, Shi E, Peroutka-Bigus N, Bellaire B, Wannemuehler M, Jergens A, Barrett T, Wu Y, Wang Q. Ex vivo Study of Telluride Nanowires in Minigut. Journal of biomedical nanotechnology. 2018; 14(5): 978-986. PMID: 29883567

7) Reding B, Carter P, Qi Y, Li Z, Wu Y, Wannemuehler M, Bratlie KM, Wang Q. Manipulate intestinal organoids with niobium carbide nanosheets. J Biomed Mater Res A. 2021; 109(4): 479-487. PMID: 32506610.

8) Cai T, Qi Y, Jergens A, Wannemuehler M, Barrett TA, Wang Q. Effects of Six Common Dietary Nutrients on Murine Intestinal Organoid Growth. PloS one. 2018; 13(2): e0191517. PMID: 29389993

9) Qi Y, Lohman J, Bratlie KM, Peroutka-Bigus N, Bellaire B, Wannemuehler M, Yoon KJ, Barrett TA, Wang Q. Vitamin C and B3 as New Biomaterials to Alter Intestinal Stem Cells. Journal of biomedical materials research. Part A. 2019;107(9):1886-1897. PMID: 31071241

10) Tong T, Qi Y, Bussiere LD, Wannemuehler M, Miller CL, Wang Q, Yu C. Transport of artificial virus-like nanocarriers through intestinal monolayers via microfold cells. Nanoscale. 2020;12(30): 16339-16347. PubMed PMID: 32725029.

11) Sun L, Rollins D, Qi Y, Fredericks J, Mansell TJ, Jergens A, Phillips GJ, Wannemuehler M, Wang Q. TNFα regulates intestinal organoids from mice with both defined and conventional microbiota. International journal of biological macromolecules. 2020; 164(1): 548-556. PMID: 32693143.

12) Chandra L, Borcherding DC, Kingsbury D, Atherly T, Ambrosini YM, Bourgois-Mochel A, Yuan W, Kimber M, Qi Y, Wang Q, Wannemuehler M, Ellinwood NM, Snella E, Martin M, Skala M, Meyerholz D, Estes M, Fernandez-Zapico ME, Jergens AE, Mochel JP, Allenspach K. Derivation of adult canine intestinal organoids for translational research in gastroenterology. BMC Biol. 2019;17(1):33. PMID: 30975131.

13) Davoudi Z, Peroutka-Bigus N, Bellaire B, Jergens A, Wannemuehler M, Wang Q. Gut Organoid as a New Platform to Study Alginate and Chitosan Mediated PLGA Nanoparticles for Drug Delivery.  Marine Drugs 2021;19(5): 282-298. PMID: 34065505.

14) Wang Q, Cheng H, Peng H, Zhou H, Li PY, Langer R. Non-genetic engineering of cells for drug delivery and cell-based therapy. Advanced Drug Delivery Reviews. 2015; 91(1):125-140. PMID: 25543006
15) Ikoba U, Peng H, Li H, Miller C, Yu C, Wang Q. Nanocarriers in therapy of infectious and inflammatory diseases. Nanoscale. 2015; 7(10):4291-305. PMID: 25680099

16) Davoudi Z, Wang Q. Intestinal Tissue Engineering with Intestinal Stem Cells. In: Wang Q, editor. Smart Materials for Tissue Engineering: Applications 1 ed. Cambridge CB4 0WF, UK: Royal Society of Chemistry; 2017. Chapter 12; p.329-357. 723p.


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