The Biology and Therapeutic Application of Mesenchymal Cells comprehensively describes the cellular and molecular biology of mesenchymal stem cells and mesenchymal stromal cells, describing their therapeutic potential in a wide variety of preclinical models of human diseases and their mechanism of action in these preclinical models. Chapters also discuss the current status of the use of mesenchymal stem and stromal cells in clinical trials in a wide range of human diseases and disorders, for many of which there are limited, or no other, therapeutic avenues.

Provides coverage on both the biology of mesenchymal stem cells and stromal cells, and their therapeutic applications
Describes the therapeutic potential of mesenchymal stem and stromal cells in a wide variety of preclinical models of human diseases and their mechanism of action in these preclinical models
Discusses the current status of mesenchymal stem and stromal cells in clinical trials in a wide range of human diseases and disorders, for many of which there are limited, or no other, therapeutic avenues
Written and edited by leaders in the field

The Biology and Therapeutic Application of Mesenchymal Cells is an invaluable resource for those studying stem cells, cell biology, genetics, gene or cell therapy, or regenerative medicine.

About the Author
Kerry Atkinson, MBBS MD DTM&H FRCP FRACP, is an Adjunct Professor at the University of Queensland Centre for Clinical Research in Brisbane, Australia, an Adjunct Professor in the Stem Cell Laboratories, Queensland University of Technology at the Translational Research Institute, Brisbane, Queensland, Australia and a Specialist in Internal Medicine at the Salisbury Medical Centre, Brisbane, Queensland, Australia.

Table of Contents

Contributors, xxvii
Editor's Preface, xxxv

Section I: An overview of mesenchymal stem cells and mesenchymal stromal cells

1 The mesenchymal stem cell, the mesenchymal stromal cell, and the mesenchymal stromal cell exosome, 3
Kerry Atkinson

2 The nomenclature of mesenchymal stem cells and mesenchymal stromal cells, 8
Armand Keating

Section II: The isolation and ex vivo expansion of mesenchymal stromal cells

3 The isolation and expansion of mesenchymal stromal cells from bone marrow, 13
Celena F. Heazlewood

4 The biology and clinical applications of mesenchymal stromal cells derived from human gestational tissues, 24
Celena F. Heazlewood

5 Human placenta-derived mesenchymal stem/stromal cells: fetal and maternal origins and critical parameters for
ex vivo expansion, 32
Rebecca A. Pelekanos and Varda S. Sardesai

Section III: The cellular and molecular biology of mesenchymal stromal cells

6 Epigenetic regulation of mesenchymal stem/stromal cell growth and multipotentiality, 41
Sarah Elizabeth Hemming, Dimitrios Cakouros, and Stan Gronthos

7 Biological changes in human mesenchymal stromal cells during monolayer culture, 58
Marietta Herrmann and Jennifer J. Bara

8 The effect of three-dimensional aggregates on the biology of mesenchymal stromal cells, 75
Yijun Liu, Ang-Chen Tsai, Xuegang Yuan, and Teng Ma

9 Cell cell signaling pathways that regulate mesenchymal stromal cell differentiation, 91
Leah Etheridge, Rebecca A. Mason, Fatima Saleh, and Paul Genever

10 Regulation of mitochondrial transport in mesenchymal stromal cells, 104
Shravani Mukherjee, Naveen K. Bhatraju, Tanveer Ahmad, and Anurag Agrawal

11 The regulation of adipogenesis from adipose-derived stem/stromal cells, 114
Lin Chen and Lei Liu

12 Modulation of osteogenic differentiation in mesenchymal stromal cells, 131
Sean Gaynard, Jessica Hayes, and Mary Murphy

13 The role of glycogen synthase kinase-3 inhibitors on bone remodeling, 148
K. Jane Escott and Patrick J. O'Shea

14 Early molecular events during in vitro chondrogenesis, 167
Tommy A. Karlsen, Rune B. Jakobsen, and Jan E. Brinchmann

15 The role of the extracellular matrix in the differentiation of mesenchymal stromal cells, 191
Peishun Shou, Qing Chen, and Yufang Shi

16 Effects of hypoxic culture on bone marrow multipotent mesenchymal stromal cells: from bench to bedside, 196
Shih-Chieh Hung

17 The role of cyclic tensile strain on osteogenesis and angiogenesis in human mesenchymal stem/stromal cells, 208
Adisri Charoenpanich, Josephine Bodle, and Elizabeth Loboa

18 The evolving concept of mesenchymal stromal cells in regenerative medicine: from cell differentiation to
secretome, 222
F.G. Teixeira, A. Pires, S.C. Serra, N. Sousa, and A.J. Salgado

19 The secretome of mesenchymal stem/stromal cells undergoing chondrogenic differentiation and those undergoing osteogenic or adipogenic differentiation, 236
Beatriz Rocha, Francisco J. Blanco, and Cristina Ruiz-Romero

20 Mesenchymal stromal cell extracellular vesicles/exosomes, 250
Ronne Wee Yeh Yeo, Ruenn Chai Lai, and Sai Kiang Lim

21 Role of tunneling nanotube crosstalk with distressed cardiomyocytes in controlling the heart repair potential of mesenchymal stromal cells, 264
Anne-Marie Rodriguez and Meriem Mahrouf-Yorgov

22 The preferential homing of mesenchymal stromal cells to sites of inflammation, 286
Catherine Sullivan

23 The role of chemokines in mesenchymal stromal cell homing to sites of inflammation, including infarcted
myocardium, 314
Shan Wang and Yaojiong Wu

24 Live cell imaging and single cell tracking of'mesenchymal stromal cells in vitro, 323
James A. Cornwell, Maria Z. Gutierrez, Richard P. Harvey and Robert E. Nordon

25 The role of mesenchymal stem/stromal cells in angiogenesis, 347
Annelies Bronckaers and Ivo Lambrichts

26 The relationship between mesenchymal stromal cells and endothelial cells, 366
Seyed Mahdi Nassiri and Reza Rahbarghazi

27 The radioresistance of mesenchymal stromal cells and their potential role in the management of radiation injury, 391
Tara Sugrue, Irene Calvo-Asensio, and Rhodri Ceredig

28 The implications of multipotent mesenchymal stromal cells in tumor biology and therapy, 415
Pratika Y. Hernanda, Maikel P. Peppelenbosch, and Qiuwei Pan

29 Mesenchymal stem/stromal cell therapy: mechanism of action and host response, 426
Aideen Ryan, Mary Murphy, and Frank Barry

30 The differences between mesenchymal stromal cells and fibroblasts, 441
Luigi Balducci, Sharon Natasha Cox, and Giulio Alessandri

31 Derivation of mesenchymal stem/stromal cells from induced pluripotent stem cells, 456
Rebecca A. Pelekanos

32 The role of mesenchymal stem cells in hematopoiesis, 467
Jean-Pierre Levesque, Rebecca N. Jacobsen, and Ingrid G. Winkler

33 The modulatory effects of mesenchymal stromal cells onthe innate immune system, 481
Ko-Jiunn Liu, Men-Luh Yen, Li-Tzu Wang, and B. Linju Yen

34 The modulatory effects of mesenchymal stromal cells on the adaptive immune system, 490
B. Linju Yen, Ko-Jiunn Liu, Men-Luh Yen, and Huey-Kang Sytwu

35 The role of mesenchymal stromal cells in the repair of acute organ injury, 496
A.A. Temnov, A.V. Vagabov, A.N. Sklifas, V.I. Novoselov, and Y.A. Belyi

36 The use of mesenchymal stromal cells in the treatment of diseases of the cornea, 524
Damien G. Harkin, Allison J. Sutherland, Laura J. Bray, Leanne Foyn, Fiona J. Li, and Brendan G. Cronin

37 The role of paracrine factors secreted by mesenchymal stromal cells in acute tissue injury, 544
Ying Wang, Tania Velletri, Chunxing Zheng, and Yufang Shi

38 Treatment of lung disease by mesenchymal stromal cell extracellular vesicles, 553
Antoine Monsel, Ying-gang Zhu, Varun Gudapati, and Jae-Woo Lee

39 Evaluating mesenchymal stem/stromal cells for treatment of asthma and allergic rhinitis, 573
Tatyana Gavrilova, Saritha Kartan, Lauren S. Sherman, Oleta A. Sandiford, and Pranela Rameshwar

40 Stem cell therapies for Huntington's disease, 581
A.T. Crane, J. Rossignol, and G. L. Dunbar

Section IV: The role of bioengineering in the therapeutic applications of mesenchymal stromal cells

41 Endometrial mesenchymal stromal cell and tissue engineering for pelvic organ prolapse repair, 601
Shanti Gurung, Jerome A. Werkmeister, and Caroline E. Gargett

42 Closed automated large-scale bioreactors for manufacturing mesenchymal stromal cells for clinical use, 616
Kerry Atkinson, Nicholas Timmins, G. Kiel, Celena Heazlewood, Michael Doran, and Gary Brooke

Section V: GMP manufacturing of mesenchymal stromal cells for clinical use

43 Current good manufacturing practice for the isolation and ex vivo expansion of mesenchymal stromal cells derived from term human placenta for use in clinical trials, 621
Kerry Atkinson, Dahlia Khalil, Celena Heazlewood, and Nina Ilic

44 A comparison of high-tier regulatory documents pertaining to biologic drugs including mesenchymal stromal cells in Australia, Europe, and the USA using a manual documentary analysis, 628
Nina Ilic

Section VI: The therapeutic application of mesenchymal stromal cells

45 The use of mesenchymal stromal cells in acute and chronic heart disease, 647
Ariel Wolf, Wayne Balkan, and Joshua Hare

46 The role of mesenchymal stem/stromal cells in the management of critical limb ischemia, 661
P.K. Gupta, Chullikana Anoop, Balasubramanian Sudha, R Mathiazhagan, Raj Swathi Sundar, and Majumdar Anish Sen

47 The role of mesenchymal stromal cells in the management of musculoskeletal disorders, 677
Stefan Zwingenberger, Ishaq Ojodu, Maik Stiehler, and Stuart B. Goodman

48 The potential role of bone marrow mesenchymal stromal cells in the treatment of ischemic stroke, 690
Yujun Pan and Ruohan Sun

49 The role of mesenchymal stromal cells in spinal cord injury, 714
P. Jendelova, L. Machova-Urdzikova, and E. Sykova

50 The role of mesenchymal stromal cells in the treatment of ulcerative colitis and Crohn's disease, 730
Céline Gregoire, Chantal Lechanteur, Alexandra Briquet, Etienne Baudoux, Olivier Giet, Olivier Delloye, Frédéric Baron, Edouard Louis, and Yves Beguin

51 Mesenchymal stromal cells targeting kidney disease: benefits of a combined therapeutic approach, 754
Brooke M. Huuskes and Sharon D. Ricardo

52 The biology and potential clinical applications of mesenchymal stromal cells in diseases of the lung, 770
Yuben P. Moodley, Jesse D. Armitage, and Dino B.A. Tan

53 The role of mesenchymal stromal cells in diseases of the lung, 787
Kerry Atkinson

54 Mesenchymal stromal cells for the treatment of'autoimmune diseases, 794
Christopher N. Lewis and Jacques Galipeau

55 The role of mesenchymal stromal cells in bacterial infection, 814
Sailaja Ghanta, Konstantin Tsoyi, and Mark A. Perrella

56 The use of mesenchymal stromal cells in solid organ transplantation, 825
Céline Gregoire, Alexandra Briquet, François Jouret, Chantal Lechanteur, Etienne Baudoux, Olivier Giet, Olivier Delloye, Frédéric Baron, Olivier Detry, and Yves Beguin

57 The role of mesenchymal stromal cells in allogeneic hematopoietic stem cell transplantation, 836
Kerry Atkinson

58 The role of mesenchymal stromal cells in the management of skin wounds, 841
Sung-Whan Kim

59 The role of mesenchymal stromal cells in skin wound healing, 845
Miao Teng and Hengshu Zhang

Section VII: Mesenchymal stromal cells as delivery vehicles for therapeutic agents

60 The role of mesenchymal stromal cells in human brain tumors, 859
Brittany C. Parker Kerrigan, Tal Shahar, Shinji Yamashita, and Frederick F. Lang

61 Mesenchymal stromal cells as gene delivery vehicles to treat nonmalignant diseases, 873
Julie R. Beegle, Jan A. Nolta, and Fernando A. Fierro

62 Gene therapy for cancer using mesenchymal stromal cells, 892
Ryosuke Uchibori and Keiya Ozawa

Section VIII: The present and the future

63 Breaking news, 901
Kerry Atkinson

64 Reconciling the stem cell and paracrine paradigms of mesenchymal stem cell function, 912
Siddaraju V. Boregowda and Donald G. Phinney

Glossary, 927

Index, 949