Organoid research in Wang Lab focuses on exploring organoids using biomaterials and nanotechnology for drug discovery and development to improve human health and longevity. In 2014, as PI of several federal 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 organoids and using synthetic foam biomaterials 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 intestinal organoids’ proliferation and differentiation ex vivo. Most interestingly, the miniguts treated with 200 ng/ml RANKL for three days were immunostained with two M-cells specific markers: 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 environments demonstrated concentration-dependent responses when exposed to inflammatory stimulants [11]. Dr. Wang and colleagues have cultured intestinal organoids from different dogs’ gut regions, either healthy or diseased [12]. He also used intestinal organoids as a new platform to study alginate and chitosan-mediated PLGA nanoparticles for drug delivery [13]. This study investigated the impact of surface charge on delivering 5-ASA loaded PLGA nanoparticles into the lumen of organoids. It was concluded that the positively charged nanoparticles were more readily transported across the epithelium into the lumen. Dr. Wang is aware of the current major non-genetic cell engineering strategies for drug delivery and cell-based therapies [14-16]. In 2022, Dr. Wang and other leaders in organoid research highlight the rationale underlying the establishment of organoid cultures and provide guiding principles for selecting suitable materials, methods, and protocols for different applications. The critical considerations for generating robust organoids have been further discussed, such as those related to cell isolation and seeding, matrix and soluble factor selection, physical cues and integration, as well as the general standards for data quality, reproducibility and deposition within the organoid community. It is a good resource for Methods and Protocols if you want to make organoids yourself [17].

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. 2014 Dec 2;1(1):37-42. doi: 10.1021/ab500041d. 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. Journal of Biomedical Materials Research. Part 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 Jan 6;7(10):4354-4360. doi: 10.1039/c4nr06377e. 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. Journal of Biomedical Materials Research. Part 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 Biology 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.

17) Zhao Z, Chen X, Dowbaj AM, Sljukic A, Bratlie K, Lin L, Fong ELS, Balachander GM, Chen Z, Soragni A, Huch M, Zeng YA, Wang Q, Yu H. Organoids. Nature Reviews Methods Primers. 2022; 2(1): 94.