Therapeutic Regeneration of Lymphatic and Immune Cell Functions upon Lympho-organoid Transplantation.

Lenti, Elisa; Bianchessi, Silvia; Proulx, Steven Thomas; Palano, Maria Teresa; Genovese, Luca; Raccosta, Laura; Spinelli, Antonello; Drago, Denise; Andolfo, Annapaola; Alfano, Massimo; Petrova, Tatiana V; Mukenge, Sylvain; Russo, Vincenzo; Brendolan, Andrea (2019). Therapeutic Regeneration of Lymphatic and Immune Cell Functions upon Lympho-organoid Transplantation. Stem cell reports, 12(6), pp. 1260-1268. Elsevier 10.1016/j.stemcr.2019.04.021

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Lymph nodes (LNs) are secondary lymphoid tissues that play a critical role in filtering the lymph and promoting adaptive immune responses. Surgical resection of LNs, radiation therapy, or infections may damage lymphatic vasculature and compromise immune functions. Here, we describe the generation of functional synthetic lympho-organoids (LOs) using LN stromal progenitors and decellularized extracellular matrix-based scaffolds, two basic constituents of secondary lymphoid tissues. We show that upon transplantation at the site of resected LNs, LOs become integrated into the endogenous lymphatic vasculature and efficiently restore lymphatic drainage and perfusion. Upon immunization, LOs support the activation of antigen-specific immune responses, thus acquiring properties of native lymphoid tissues. These findings provide a proof-of-concept strategy for the development of functional lympho-organoids suitable for restoring lymphatic and immune cell functions.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Proulx, Steven Thomas

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2213-6711

Publisher:

Elsevier

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

13 Nov 2019 11:22

Last Modified:

13 Nov 2019 11:22

Publisher DOI:

10.1016/j.stemcr.2019.04.021

PubMed ID:

31155505

Uncontrolled Keywords:

lymphatic system lympho-organoids lymphoid tissue development preclinical mouse models stromal cell biology tissue engineering tissue regeneration

BORIS DOI:

10.7892/boris.134690

URI:

https://boris.unibe.ch/id/eprint/134690

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