Difference between revisions of "User:Christina Katherine Bray/Notebook/Muscle Regeneration Using Ecto-MSCs"

From OpenWetWare
Line 76: Line 76:
** This research proposal is a class project for the Laboratory Fundamentals of Biological Engineering (20.109) class at the Massachusetts Institute of Technology taught in Spring 2014.
* This research proposal is a class project for the Laboratory Fundamentals of Biological Engineering (20.109) class at the Massachusetts Institute of Technology taught in Spring 2014.

Revision as of 15:32, 5 May 2014

Project Overview

This project focuses on stem cell engineering and differentiation into different types of muscle tissue (skeletal muscle, smooth muscle, and cardiac muscle) for transplant/regeneration. This research aims to address the social problem that many cases of muscle damage do not yet have good treatments; for example, patients with severe heart muscle damage often undergo invasive heart transplants and patients with skeletal muscle damage often go undiagnosed or untreated and the damage heals as scar tissue, often causing permanent pain or mobility limitations. On a scientific level, stem cells could not be induced to develop into functional muscle tissue until very recently, and there are still many problems with the approach that need to be dealt with in order for it to become a viable treatment for humans. These are the issues that our project seeks to address.

Background Information

This section is a work in progress.

Research Problem and Goals

Tissue engineering of mesenchymal stem cells and/or skeletal muscle-derived stem cells to induce differentiation into three major types of muscle tissue (skeletal muscle, smooth muscle, and cardiac muscle). Our goal is to narrow down the most effective methods to generate all types of muscle tissue in vitro, in order to lead to the development of strategies to repair injured muscle.

Project Details and Methods

This section is a work in progress.

Predicted Outcomes

This section is a work in progress.

Needed Resources

This section is a work in progress.

Potential Societal Impact

This section is a work in progress.


1) Xin Nie, Yongjun Xing, Manjin Deng, Li Gang, Rui Liu, Yongjie Zhang, Xiujie Wen. (2014) Ecto-Mesenchymal Stem Cells from Facial Process: Potential for Muscle Regeneration. Cell Biochemistry and Biophysics. http://link.springer.com/article/10.1007%2Fs12013-014-9964-x/fulltext.html

This study focuses on the differentiation of ecto-MSCs in regenerating muscle tissue. EMSCs help in the formation of teeth, salivary glands, and muscle tissue in early development, and thus it was hypothesized that the transplantation of EMSCs might induce them to differentiate into mature skeletal muscle. It was discovered that EMSCs, in mice and therefore potentially in humans, can accumulate and form myotubes and continue differentiating into skeletal muscle when in a sheet of cells in vitro, so there is potential for cell therapy and engineering tissue that can repair skeletal muscle.

2) Rui-feng Qin, Tian-qiu Mao, Xiao-ming Gu, Kai-jing Hu, Yan-pu Liu, Jin-wu Chen, Xin Nie. (2007) Regulation of skeletal muscle differentiation in fibroblasts by edogenous MyoD gene in vitro and in vivo. Molecular and Cellular Biochemistry. http://link.springer.com/article/10.1007%2Fs11010-007-9446-1

This study provided an analysis of how myogenic regulatory factors (MRFs), and specifically MyoD helps regulate skeletal muscle differentiation. NIH3T3 cell lines (embryonic mice fibroblasts) were transfected such that exogenous MyoD was expressed at high levels. When grown in vivo (in mice) and in vitro, the fibroblasts underwent myogenesis and remained stable, so it was concluded that MyoD may play an important role in cell-mediated gene therapy of skeletal muscle.

3) Stella Alimperti, Hui You, Teresa George, Sandeep K. Agarwal, Stelios T. Andreadis. (2014) Cadherin-11 regulates mesenchymal stem cell differentiation into smooth muscle cells and development of contractile function in vivo. Journal of Cell Science. http://jcs.biologists.org/content/early/2014/04/13/jcs.134833.long

MSC differentiation toward smooth muscle cell (SMC) can be induced by some soluble factors, such as Transform Growth Factor beta 1 (TGF-β1) but is also influenced by adherent junctions. This study found that Cadherin-11 but not Cadherin-2 was necessary for MSC differentiation into SMC by influencing TGF-β receptor II pathway as well as a Rho-associated protein kinase pathway and inducing contractile function both in vitro and in vivo.

4) Wei Huang, Din-Zhang Xiao, Yigang Wang, Zhi-Xin Shan, Xiao-Ying Liu, Qiu-Xiong Lin, Min Yang, Jian Zhuang, Yangxin Li, Xi-Yong Yu. (2014) Fn14 Promotes Differentiation of Human Mesenchymal Stem Cells into Heart Valvular Interstitial Cells by Phenotypic Characterization. Journal of Cellular Physiology. http://onlinelibrary.wiley.com/doi/10.1002/jcp.24480/abstract;jsessionid=15D39A090EF3CAEC4688DFE9AA258621.f03t01

This study focused on using bone marrow derived MSCs and vectors that over express the fibroblast inducible factor 14 (Fn14) gene in order to see if they could induce differentiation into cells used in heart valves. It was found that the expression of α-smooth muscle actin (SMA) was significantly higher with Fn14, and the phenotype of these in vitro cells were similar to the phenotype of normal heart valves, so this may provide a therapeutic strategy for heart valve disease treatment.

5) Jason Tchao, Jong Jin Kim, B. Lin, G. Salama, C.W. Lo, L. Yang, Kimimasa Tobita. (2013) Engineered Human Muscle Tissue from Skeletal Muscle Derived Stem Cells and Induced Pluripotent Stem Cell Derived Cardiac Cells. International Journal of Tissue Engineering. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984572/#__ffn_sectitle

In this study, they experimented whether muscle differentiated from skeletal muscle derived stem cells (MDSCs) can express phenotypes (such as sarcomere proteins and transcription factors) shared between developing cardiac and skeletal muscle cells. They compared engineered muscle tissue derived from MDSCs to induced pluripotent stem cell-derived cardiac cells (iPS-EMT), and found that MDSCs can differentiate into muscle cells that mimic both developing cardiac and skeletal muscle which could possibly lead to therapeutic options of MDSCs in cardiac repair treatment.

6) Lin Wang, Lan Cao, Janet Shansky, Zheng Wang, David Mooney, Herman Vanderburgh. (2014) Minimally invasive approach to the repair of injured skeletal muscle with a shape-memory scaffold. Molecular Therapy. http://www.nature.com/mt/journal/vaop/naam/abs/mt201478a.html

Repairing injured skeletal muscle by cell therapy is a result of injected cells, but cell survival has typically been low. This study designed a degradable scaffold that can be implanted, in addition to the delivery of myoblasts and growth factors, that promoted the survival of cells in vivo and thus the functional regeneration of injured skeletal muscle.

7) Fiona C. Lewis, Beverly J. Henning, Giovanna Marazzi, David Sassoon, Georgina M. Ellison, Bernardo Nadal-Ginard. (2014). Porcine Skeletal Muscle-Derived Multipotent PW1pos/Pax7neg Interstitial Cells: Isolation, Characterization, and Long Term Culture. Stem Cells Translational Medicine. http://stemcellstm.alphamedpress.org/content/early/2014/04/17/sctm.2013-0174.long

This study isolated skeletal muscle-derived interstitial progenitor cells and started to explore the potential of these cells for use in tissue engineering and muscle regeneration from a single multipotent stem cell type. They show that these cells can give rise to skeletal myoblast/myotubes, smooth muscle, and cardiomyocyte-like cells, which indicates that skeletal muscle (an easily accessible source) may be able to help regenerate other types of muscle tissue.

8) Akira Ito, Yasunori Yamamoto, Masanori Sato, Kazushi Ikeda, Masahiro Yamamoto, Hideaki Fujita, Eiji Nagamori, Yoshinori Kawabe, Masamichi Kamihira. (2014). Induction of functional tissue-engineered skeletal muscle constructs by defined electrical stimulation. Scientific Reports. http://www.nature.com/srep/2014/140424/srep04781/full/srep04781.html

Because electrical impulses are necessary for skeletal muscle development in vivo, this study explored the idea of using electrical stimulation (and attempted to optimize a protocol) to fabricate functional skeletal muscle tissue in vitro, which may be used for therapies to restore damaged muscle.

9) Mark Juhas, George C. Engelmayr Jr., Andrew N. Fontanella, Gregory M. Palmer, Nenad Bursac. (2014). Biomimetic engineered muscle with capacity for vascular integration and functional maturation in vivo. PNAS. http://www.pnas.org/content/111/15/5508.long

This study describes the creation of biomimetic skeletal muscle tissues with phenotypes (structural/functional/myogenic properties) characteristic of native muscle tissue that also can be implanted in vivo for restoration. They also state that the implantation process is enhanced by formation of muscle architecture in vitro.


  • This research proposal is a class project for the Laboratory Fundamentals of Biological Engineering (20.109) class at the Massachusetts Institute of Technology taught in Spring 2014.