Cell Therapy for the Enhancement of Bone Repair - Engineered Bone: Tissue Engineering Intelligence Unit - page 154

Many of these issues could be solved by a Tissue Engineering approach to bone repair. 15,16
Stem cell science is advancing vigorously as well as biomaterial science. 17,18 The knowledge of
soluble signalling molecules and transcription factors regulating the cellular events leading to
osteogenic differentiation and finally to bone repair will soon lead to the understanding of the
key mechanism involved. 19-21 Already experimental studies both preclinical and clinical shade
light on the enormous potential of this new discipline in regenerative medicine. 22-25
Here we review the impact of recent work in this interdisciplinary field on the treatment of
skeletal lesions. We will present and discuss the cell based strategy for bone reconstruction.
After introducing the “clinical scenario”, we will present the major players in the game:
osteoprogenitor cells and their potential sources, scaffolds and strategies for cell delivery as well
as preclinical experimental models and clinical pilot studies.
Clinical Scenario
Bone lesions/defects occur in a wide variety of clinical situations, and their reconstruction
to provide mechanical and functional integrity is a necessary step in the patient's rehabilitation.
Moreover, a bone graft or a bone substitute is often required in maxillo-facial and orthopedic
surgery to assist healing in the repair of osseous congenital deformities, or in the repair of
defects due to trauma or to surgical excision after elimination of osseous disease processes
exceeding a certain size.
Modern therapeutic approaches to repair large bone defects can be divided into two main
groups: the first excluding (Ilizarov and bone transport) and the second including graft trans-
plant (auto-, allo- and xeno- grafts; different biomaterial implants).
Osteotomy followed by bone distraction, the Ilizarov technique, lays on the bone regenera-
tion potential. This apporach circumvents all problems related to bone grafts, but it is highly
inconvenient to the patient. The relatively high rate of success obtained with this technique is
counterbalanced by the long recovery time and the high rate of complications. 26,27
Bone auto-grafts, both nonvascularized and vascularized, are considered at the moment the
optimal choice. Presently vascularized grafts are the most widely used, being considered as the
most successful. The success rate is high indeed, but complications, such as infections, non
unions etc. are very frequent especially in large shaft reconstructions. 6-8 Furthermore, large
reconstructions with autologous bone require large harvests of healthy tissue with important
donor site morbidity. 10-12 Therefore this approach is limited by definition.
Many of the problems presented by the autografts, in particular the immediate availability
of tissue for transplant, could be solved by allo- and possibly xeno-grafts. Host immune re-
sponses to and potential risk of infectious diseases transmission by bone allo- and xeno -grafts
raise several concerns limiting their applications.
Novel materials, cellular transplantation and bioactive molecule delivery are being explored
alone and in various combinations to address the problem of bone deficiency. The aim of these
strategies is to exploit the body's natural ability to repair injured bone with new bone tissue,
and later to remodel the newly formed bone in response to the local stresses it experiences. In
general, the strategies discussed in this paper attempt to provide the reconstructed region with
appropriate initial mechanical properties, encourage new bone to form in the region, and then
gradually degrade to allow the newly formed bone to remodel and acquire the proper mechani-
cal support function. Several of the concepts presented below are already finding initial clinical
applications in early patient trials.
Sources of Osteoprogenitor Cells
Osteoprogenitor cells have been isolated from a variety of tissues, including periostium,
bone marrow, spleen, thymus, skeletal muscle, adipose tissue, skin and retina. 28-39 Recently
osteoprogenitors have also been reported to be isolated from peripheral blood, although with
very low efficiency. 40 These findings shade new light into stem cell biology and cellular differ-
entiation. However, their use for tissue engineering is not always straightforward. For this