Mesenchymal Stem Cells and Skeletal Regeneration

By Peter Giannoudis, Elena Jones, Xuebin Yang and Dennis Mcgonagle

Mesenchymal Stem Cells and Skeletal Regeneration covers our current understanding of the role of mesenchymal stem cells (MSCs) and other mesenchymal progenitors in skeletal regeneration, encompassing bone, cartilage and whole joint regeneration. The expansion reflects developments in the field to include data on the use of MSCs in drug development, growth factors, scaffolds and biomechanical manipulations for skeletal trauma and diseases, including osteoporosis and arthritis.

Written for an audience of clinicians and young researchers who are exposed to MSCs in their work, this work summarizes recent findings pertaining to the definition and characterization of MSCs in skeletal tissues and discusses the mechanisms of their actions in regeneration of bone in vivo. The authors describe recent findings pertaining to the efficacy of MSC therapies in animal models and in human clinical trials and bring together literature showing that the ways MSCs are extracted, expanded and implanted can considerably affect bone formation outcomes. Finally, it presents the latest knowledge on the nature of native MSCs in skeletal tissues, which provide a platform for novel in situ tissue regeneration approaches for systemic bone disease such as osteoporosis.

• Focuses specifically on the use of stem cells in skeletal tissue generation for a broad audience of stem cell, cancer, and bone biologists, orthopedists, oncologists, and regenerative medicine specialists
• Provides a short historical ‘detour’ and foundational information on founding concepts, discoveries and personalities in MSC research
• Assists a new generation of scientists and clinicians in digesting the multitude of journal articles on the topic by providing easily-absorbed and condensed foundational context

• Language: English
• Publisher: Academic Press
• Release date: Feb 20, 2013
• ISBN: 9780124081314

Book preview

Mesenchymal Stem Cells and Skeletal Regeneration

Elena Jones

Peter Giannoudis

Xuebin Yang

Dennis McGonagle

Table of Contents

Cover image

Title page

Copyright

Chapter 1. Current Strategies for Skeletal Regeneration in the Early Twenty-First Century

1.1 The Economic and Social Burden of Diseases Affecting Bone and Cartilage

1.2 Current Clinical Approaches for Bone Regeneration: The Diamond Concept

Chapter 2. Mesenchymal Stem Cells: Discovery in Bone Marrow and Beyond

2.1 Discovery

2.2 Explosion of Interest in MSCs

2.3 MSC Tissue Heterogeneity

Chapter 3. Traditional Bone Tissue Engineering Using MSCs

3.1 Proof-of-Principle Experiments in Animal Models

3.2 Cell Therapy Using MSCs

3.3 Bone Tissue Engineering

3.4 Serum-Free MSC Expansion

3.5 Osteochondral Tissue Repair

Chapter 4. Challenges for Cartilage Regeneration

4.1 Osteoarthritis (OA) Development and the Loss of Cartilage

4.2 Current Cartilage Repair Strategies

4.3 Spontaneous Cartilage Repair

4.4 Harnessing the Potential of Synovial Fluid MSCs for Cartilage Repair Applications

Chapter 5. Animal Models for Investigating MSC Involvement in Bone and Cartilage Repair

5.1 Small Animal Models

5.2 Large Animal Models for Bone Repair and Regeneration

5.3 Animal Models for Osteochondral Tissue Engineering

5.4 Animal Models for Cartilage Tissue Engineering

Chapter 6. Native MSCs

6.1 MSCs and Marrow Reticular Cells

6.2 Nonadherent MSCs

6.3 Solid Tissues: MSCs and Fibroblasts

6.4 MSC as a Pericyte

Chapter 7. Trophic Actions of MSCs

7.1 Discovery of the Trophic Action of MSCs in Cardiac Repair Trials

7.2 Other Disease Applications

Chapter 8. Novel Approaches for Bone Regeneration Targeting Native MSCs

8.1 Medical Devices Allowing MSC Concentration

8.2 Host MSC Modifiers

8.3 In vivo Bioreactors and Periosteum-Like Membranes

8.4 Targeting MSCs in Systemic Bone Diseases: Novel Bone Anabolics

Concluding Remarks

References

Copyright

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First published 2013

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ISBN: 978-0-12-407915-1

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Chapter 1

Current Strategies for Skeletal Regeneration in the Early Twenty-First Century

1.1 The Economic and Social Burden of Diseases Affecting Bone and Cartilage

There is a growing number of clinical conditions, in which the normal process of skeletal regeneration is impaired. In health, the maintenance of stable bone mass is the result of a carefully controlled balance between the activities of bone-forming osteoblasts and bone-resorbing osteoclasts [1, 2]. In the clinical setting, the most common form of intrinsic bone regeneration is fracture healing; however, approximately 10% of fractures fail to heal and require additional interventions [3]. In orthopedic surgery, there are other conditions that require bone regeneration in high quantity, for example, bone reconstruction after tumor resection or after large loss of bone due to infection, trauma, or skeletal abnormality [4]. In dental and maxillofacial applications, the bone often needs strengthening prior to dental implant surgery and in some cases, large fragments of bone require rebuilding following injuries to the head. In some conditions, such as avascular necrosis, the innate regenerative process is compromised, leading to disability, with current surgical treatments failing to provide long-term improvements [4, 5].

Furthermore, there exist systemic bone abnormalities such as osteoporosis (OP), which is one of the commonest diseases among older females. It is characterized by disequilibrium of bone formation and resorption, leading to weakening of bone, which in turn contributes to the increased risk of fractures [6]. With mortality rates of 30% at 1 year post injury, OP fragility fractures pose a great challenge to both social and insurance-based healthcare economies, with the annual UK costs alone estimated to be in a region of £2 billion [7]. Another very common musculoskeletal age-related disorder is osteoarthritis (OA), the disease affecting both bone and cartilage, which similarly causes considerable morbidity and mortality [8, 9]. With a prevalence of hip OA reported to be reaching 8% [10], indirect costs, due to OA-related workday absences, lead to significant loss in productivity in the Western economies [11]. Currently, OA is treated only symphomatically, with the ultimate solution to alleviate pain being joint replacement surgery. Equally, despite recent advances in the treatment of OP using drugs targeting the osteoclastic lineage [4, 6], these drugs can lead to a low bone turnover state and reduced osteoblastic activity [12]; therefore, the disease remains a major health burden to the European economies.

1.2 Current Clinical Approaches for Bone Regeneration: The Diamond Concept

The current management of complex clinical situations in which the normal process of skeletal regeneration is impaired involves a number of treatment methods that alone, or in combination, lead to the enhancement of innate healing processes [13]. In relation to repairing bone, four equally-important factors