Cell Therapy for the Enhancement of Bone Repair - Engineered Bone: Tissue Engineering Intelligence Unit - page 153

C HAPTER 11

Cell Therapy for the Enhancement
of Bone Repair

Hervé Petite and Rodolfo Quarto

Abstract

At variance with cartilage, bone displays an important potential of self- repair and

regeneration. In vivo and in physiological conditions, this process occurs through strictly
regulated sequences of cellular events. Successful replacement of bone through tissue
engineering likely will be dependent on the recapitulation of this cascade of events. Bone re-
generation in fact requires the cross-talk between microenvironmental factors and cells, where
mesenchymal progenitor cells are recruited and properly guided by soluble signalling mol-
ecules and extracellular matrix. Tissue engineered bone repair have attempted to mimic this
natural setting by delivering a source of cells capable of differentiating into osteoblasts, induc-
tive growth factors, and bioresorbable scaffolding matrices to support cellular attachment, mi-
gration, proliferation and fate. Engineered tissue repair may in fact be viewed as the restoration
of form and function to injured bone as well as to other tissues. The manipulation of these
elements for therapeutic purposes might become common clinical practice.
The development of cell therapy approaches has dramatically improved in recent years as
the understanding of musculoskeletal stem cell biology advances. Synthetic biomaterials devel-
oped by the industry are used to exploit skeleton's capacity to regenerate and repair. Sophisti-
cated experimental designs have tried to combine two or more of these elements.
Many issues in this innovative field remain to be solved of course, but cell based therapies
for the repair of relevant bone defects are not far from routine clinical feasibility. This chapter
will attempt to highlight the development of cell based approaches for bone tissue engineering.

Introduction
Bone repair is possibly one of, if not the oldest challenge that the medical culture has been
facing since the dawn of the history of medicine. 1,2 In particular, the reconstruction of large
bone segments has always represented a major clinical issue, both for frequency and for diffi-
culty of reconstruction. With the exception of the Ilizarov technique, all methods proposed for
bone repair are based on a concept of “part substitution”. The substituting “spare part” has to
become vascularized and vital in order to be integrated in and substituted by the host tissue in
order to heal the lesion. This is a difficult task to achieve when cortical bone grafts from tissue
banks are used, 3-5 and represents a major problem even with autologous vascularized grafts. 6-8
Failure and complications are indeed very frequent, 9 besides the complexity of the surgery and
the donor site morbidity in the case of autografts. 10-12 The use of bone allografts, which could
solve a number of problems, raises further concerns about the possible transmission of infec-
tious diseases and of immune responses by the host organism. 9,13,14 Because of all these con-
cerns, orthopedic surgeons often adopt solutions that do not allow a complete functional re-
covery and in some cases they have to take drastic measures such as arthrodesis or limb
amputation.