Page 307 - IJB-9-3

International Journal of Bioprinting

RESEARCH ARTICLE
Bioprinted Notch ligand to function as stem

cell niche improves muscle regeneration in
dystrophic muscle

Zewei Sun , Xianlin Yue , Lei Liu , Ying Li , Jie Cui , Dong Li , Lee Weiss ,
1
2
3
1
1†
1†
1
Phil Campbell , Yanling Mu *, Johnny Huard *, Xiaodong Mu *
1
3
4
1
1 Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
2 Cryomedicine Lab, Qilu Hospital of Shandong University, Jinan, Shandong, China
3 The Robotics Institute, Carnegie Mellon University, Pittsburgh, PA, USA
4 Center for Regenerative Sports Medicine, Steadman Philippon Research Institute, Vail, CO, USA
(This article belongs to the Special issue: Advances in 3D bioprinting and biofabrication of biomaterials)
Abstract
In Duchenne muscular dystrophy, dystrophic muscle phenotypes are closely
associated with the exhaustion of muscle stem cells. Transplantation of muscle
stem cells has been widely studied for improving muscle regeneration, but poor
cell survival and self-renewal, rapid loss of stemness, and limited dispersion of
grafted cells following transplantation have collectively hindered the overall
† These authors contributed equally
to this work. success of this strategy. Optimized mechanisms for maintaining and improving
stem cell function are naturally present in the microenvironment of the stem cell
*Corresponding authors: niche in healthy muscles. Therefore, one logical strategy toward improving stem cell
Xiaodong Mu
(muxiaodong@sdfmu.edu.cn) function and efficiency of stem cell transplantation in diseased muscles would be the
Yanling Mu establishment of a microenvironment mimicking some key aspects of healthy native
(muyanling@sdfmu.edu.cn) stem cell niches. Here, we applied inkjet-based bioprinting technology to engineer a
Johnny Huard mimicked artificial stem cell niche in dystrophic muscle, comprising stem cell niche
(jhuard@sprivail.org) regulating factors (Notch activator DLL1) bioprinted onto 3D DermaMatrix construct.
Citation: Sun Z, Yue X, Liu L, et al., The recombinant DLL1 protein, DLL1 (mouse): Fc (human) (rec), was applied here
2023, Bioprinted Notch ligand to as the Notch activator. Bioprinted DermaMatrix construct was seeded with muscle
function as stem cell niche improves
muscle regeneration in dystrophic stem cells in vitro, and increased stem cell maintenance and repressed myogenic
muscle. Int J Bioprint, 9(3): 711. differentiation process was observed. DLL1 bioprinted DermaMatrix construct was
https://doi.org/10.18063/ijb.711 then engrafted into dystrophic muscle of mdx/scid mice, and the improved cell
Received: November 28, 2022 engraftment and progression of muscle regeneration was observed 10 days after
Accepted: January 18, 2023 engraftment. Our results demonstrated that bioprinting of Notch activator within 3D
Published Online: March 16, 2023
construct can be applied to serve as muscle stem cell niche and improve the efficacy
Copyright: © 2023 Author(s). of muscle stem cell transplantation in diseased muscle.
This is an Open Access article
distributed under the terms of the
Creative Commons Attribution Keywords: Muscle dystrophy, Stem cell niche, Muscle stem cell, Notch signaling
License, permitting distribution
and reproduction in any medium,
provided the original work is
properly cited.
1. Introduction
Publisher’s Note: Whioce
Publishing remains neutral with During the regeneration of injured or diseased skeletal muscle, the deposition of
regard to jurisdictional claims in scar tissue (fibrosis) often dominates the healing process when stem cells become
published maps and institutional
affiliations. dysregulated or depleted. Indeed, the depletion of functional muscle stem cells has been

Volume 9 Issue 3 (2023) 299 https://doi.org/10.18063/ijb.711