The Synthetic Artificial Stem Cell (SASC): Shifting the Paradigm of Cell Therapy in Regenerative Engineering

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2022 Jan 6

PMID 34987101

Citations 13

Authors

Shiv Shah

Caldon Jayson Esdaille

Maumita Bhattacharjee

Ho-Man Kan

Cato T Laurencin

Affiliations

Soon will be listed here.

Abstract

Stem cells are of great interest in tissue regeneration due to their ability to modulate the local microenvironment by secreting bioactive factors (collectively, secretome). However, secretome delivery through conditioned media still requires time-consuming cell isolation and maintenance and also may contain factors antagonistic to targeted tissue regeneration. We have therefore engineered a synthetic artificial stem cell (SASC) system which mimics the paracrine effect of the stem cell secretome and provides tailorability of the composition for targeted tissue regeneration. We report the first of many applications of the SASC system we have formulated to treat osteoarthritis (OA). Choosing growth factors important to chondrogenesis and encapsulating respective recombinant proteins in poly (lactic-coglycolic acid) 85:15 (PLGA) we fabricated the SASC system. We compared the antiinflammatory and chondroprotective effects of SASC to that of adipose-derived stem cells (ADSCs) using in vitro interleukin 1B-induced and in vivo collagenase-induced osteoarthritis rodent models. We have designed SASC as an injectable therapy with controlled release of the formulated secretome. In vitro, SASC showed significant antiinflammatory and chondroprotective effects as seen by the up-regulation of SOX9 and reduction of nitric oxide, ADAMTS5, and PRG4 genes compared to ADSCs. In vivo, treatment with SASC and ADSCs significantly attenuated cartilage degeneration and improved the biomechanical properties of the articular cartilage in comparison to OA control. This SASC system demonstrates the feasibility of developing a completely synthetic, tailorable stem cell secretome which reinforces the possibility of developing a new therapeutic strategy that provides better control over targeted tissue engineering applications.

Citing Articles

Classes of Stem Cells: From Biology to Engineering.

Shah S, Ghosh D, Otsuka T, Laurencin C Regen Eng Transl Med. 2024; 10(3):309-322.

PMID: 39387056 PMC: 11463971. DOI: 10.1007/s40883-023-00317-x.

Animal Models of Osteoarthritis: Updated Models and Outcome Measures 2016-2023.

Chapman J, Ghosh D, Attari S, Ude C, Laurencin C Regen Eng Transl Med. 2024; 10(2):127-146.

PMID: 38983776 PMC: 11233113. DOI: 10.1007/s40883-023-00309-x.

Microfragmented abdominal adipose tissue-derived stem cells from knee osteoarthritis patients aged 29-65 years demonstrate in vitro stemness and low levels of cellular senescence.

Hammer F, Holmich P, Nehlin J, Vomstein K, Blond L, Holmich L J Exp Orthop. 2024; 11(3):e12056.

PMID: 38911188 PMC: 11190460. DOI: 10.1002/jeo2.12056.

A programmable arthritis-specific receptor for guided articular cartilage regenerative medicine.

Walton B, Shattuck-Brandt R, Hamann C, Tung V, Colazo J, Brand D bioRxiv. 2024; .

PMID: 38352576 PMC: 10862827. DOI: 10.1101/2024.01.31.578281.

Strategies for Constructing Tissue-Engineered Fat for Soft Tissue Regeneration.

Zhao J, Lu F, Dong Z Tissue Eng Regen Med. 2023; 21(3):395-408.

PMID: 38032533 PMC: 10987464. DOI: 10.1007/s13770-023-00607-z.

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