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Adult Mesenchymal Stem Cells: Biological Properties, Characteristics,

and Application in Maxillofacial Surgery

INDIAN DENTAL ACADEMYLeader in continuing Dental Education


• The purpose of this article is to review the literature on the biology of adult tissue-dervied mesenchymal stem cells and their potential in maxillofacial surgery.

• Mesenchymal stem cells are multipotent cells cabable of giving rise to cells of mesodermal origin, including bone, cartilage, fat, tendon ,and muscle, making this cell promising candidates for cell-based tissue engineering for the repair of lost or damaged maxillofacial tissues


Mesenchymal Stem Cells: Biological Properties and Characteristics

• Background: Friedenstein et al proposed that BM of postnatal organism also contained non hemopoietic adherent fibroblastic cells capable of giving rise to bones and cartilage like colonies. Apart from BM other sources of MSCs periosteum, synovial membrane, muscle, fat, vascular pericytes, peridontal ligament,deciduous teeth, dermis

• In Vitro : The clinical applicability of MSCs is further enhanced by their immunological properties . MSCs are generally described as nonimmunogenic, based on their MHC class1, MHCclass2, CD40, CD80, CD86 phenotype& immune tolerance. MSC mediated immune suppresion, interesting observation have been made on the immunomodulatory effects of MSCs in vivo . For instance, the survival of allogeneic skin grafts was shown to be prolonged by the intravenous administration of MSCs in immunocompetent, outbred baboons. The immunotolerance and the immunomodulatory properties of MSCs thus augment their potential as a progenitor cell source for clinical applications.

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Multilineage Differentiation Potential


Cell-Based Tissue Engineering Tissue engineering is an emerging interdisciplinary field that applies principles of both life sciences and engineering towards the development of biological substitute that restores, maintain, and improve function of damaged and/ or lost tissues. The basic concept of stem cell-based tissue engineering, as illustrated in the figure, consist of cell isolation and expansion, followed by a reimplantation procedure in combination with a scaffolding material


MSCs provides an ideal cell source for maxillofacial tissue engineering for the following reasons

• Their use is not complicated by ethical and legal controversies.

• They are generally considered to be easily accessible and readily available.

• They possess extensive self-renewal or expansion capability.

• They have the capacity to differentiate readily into cell types relevant to maxillofacial region.

• They possess little to no immunogenic or tumorigenic potential.


Parameters of an ideal scaffolding material

• Surface Area• Porosity• 3-dimensional architecture• Degradation characteristics• Mechanical integrity• Biocompatibility• Ability to support cell proliferation, differentiation,

angiogenesis, and matrix deposition.


Candidate scaffolding materials

• Natural Alginate Collagen• Synthetic Polycaprolactone PLA-PGA Human BM-derived MSCs seeded on prefabricated 3-dementional

Polycaprolactone(200-700 nm porosity and range of 5-475 micrometer) nanofibrous scaffolds were efficiently induced to undergo osteogenesis, chondrogenesis, and adipogenesis.


Gene Therapy And Tissue Engineering

• Ability of MSCs to be transduced, gives them the potential to serve as vehicles for either long-term or short-term therapeutic gene transfer for instance, as in expressing BMP for bone repair or the delivery of chemotherapeutics(eg, Interferon- β). This was validated by “Chang et al”

• “Peterson et al” demonstrated that human BM-derived MSCs infected with a BMP-2 containing Adenovirus has also been shown to enhance anterior anterior spine fusion in a porcine model.

• Administration of supraphysiological doses of BMP has been shown to induce bone resorption .


Application in Maxillofacial Surgery• Cranifacial Skeleton “Warnke et al” showed that custom designed titanium mesh tray

was packed with BMP, Bone mineral blocks, and a BM aspirate was implanted in patient’s Lattismus dorsi muscle, harvested after seven weeks, and used as a free-tissue transfer to repair a mandibular defect, the neo mandible resulted in new bone formation and improved mastication.

“Lendeckel et al” reported that a 7-year girl sufferring from widespread calverial defect was treated with the use of 2 large, resorbable macroporous sheets and adipose-derived stem cells, after 3 months CT scan new bone formation and near complete calvarial continuity .

“Qi et al” reported the effect of MSCs in Distraction Osteogenesis in rat model . After distraction BM-derived MSCs were injected in the gap while the control group were injected with saline , the animal were sacrificed on day 27 and 55 , the radiographic finding showed higher radiodensity in experimental than control group, increased bone density in histomorphometric analysis and new Trabeculae.


• Temperomandibular Joint Reconstruction

Alhadlaq and Mao reported the development of mandibular condyle was enhanced by differentiating MSCs into both Osteogenic and Chondrogenic lineages, more accurately mimicking the developmental process of mandibular condyle was engineered from rat MSCs encapsulated in PEGDA (poly ethtlene glycol diacrylate).

The same population of MSCs are treated separately with chondrogenic and osteogenic induction medium in culture, after which the cells were photoencapsulated as 2 separate stratified layers within the PEGDA.

The cell laden construct were then implanted in dorsum of an immunodefeciant mouse . After 8 weeks of in vivo implantation, histological examination revealed 2 stratified layers of cartilagenous and osseous phenotype in construct.