Regenerative Facial Reconstruction of Terminal Stage Osteoradionecrosis and Other Advanced Craniofacial Diseases with Adult Cultured Stem and Progenitor Cells

Head and Neck Surgery Unit, POLUSA Hospital, Lugo, Spain.
Plastic and Reconstructive Surgery (Impact Factor: 2.99). 11/2010; 126(5):1699-709. DOI: 10.1097/PRS.0b013e3181f24164
Source: PubMed


Treatment options in cases of severe craniofacial disorders with bone loss and tissue damage are usually limited to vascularized and nonvascularized tissue transfers, allografts, mechanical devices and, more recently, facial transplantation. Despite the therapies available, the demand for new approaches is realized in cases where current therapies are unable to resume form and function. This study presents the feasibility of alternative treatments based on cultured bone marrow cells that yield mixed populations of mesenchymal, hematopoietic, and endothelial lineages at very early stages implemented as part of a novel regenerative procedure.
One hundred milliliters of a bone marrow aspirate was inoculated into the automated single-pass perfusion technology system, AastromReplicell, for the development of the cellular product, tissue repair cells. After 12 days of incubation, cells were exposed to a specially designed osteogenic environment in an autogenous fibrin-rich and platelet-rich clot and membrane with a mineral base of β-tricalcium phosphate and hydroxyapatite.
A case of maxillary and mandibular radionecrosis (stage IIIR) with pathologic fracture presented early osteogenesis, total recovery from alveolar nerve anesthesia, facial nerve reinnervation, and skin regeneration. Another case with nonhealed fracture, bone loss, and bilateral paresthesia demonstrated callus formation, bone regeneration, and nerve recovery. Finally, maxillary bone regenerated after massive deficiency. Oral functional restoration with implants and fixed prosthesis was accomplished in all cases.
After nerve, bone, skin, and vessel formation in three patients with severe abnormality, bone marrow-derived mixed cultured stem cell lineages could be considered a new paradigmatic approach to advanced disease.

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    • "STATs are activated after injury. Selected cytokines and growth factors such as IL-6, LIF, CNTF, G-CSF, G-CSFR, EPO, EGF, IGF-1, NGF withdrawal, BDNF, free radicals , excitatory neurotransmitters and other inflammatory mediators activate the signaling pathway in nerve injury [6] [15] [16] [19] [27]. Schwann cells along with direct proximity of injured nerve fibers can accumulate along axons which are related to the regeneration process. "
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    ABSTRACT: The facial nerve (VII) is one of the most important cranial nerves for head and neck surgeons. Its function is closely related to facial expressions that are individual for every person. After its injury or palsy, its functions can be either impaired or absent. Because of the presence of motor, sensory and parasympathetic fibers, the biology of its repair and function restoration depends on many factors. In order to achieve good outcome, many different therapies can be performed in order to restore as much of the nerve function as possible. When rehabilitation and physiotherapy are not sufficient, additional surgical procedures and therapies are taken into serious consideration. The final outcome of many of them is discussable, depending on nerve damage etiology. Stem cells in facial nerve repair are used, but long-term outcomes and results are still not fully known. In order to understand this therapeutic approach, clinicians and surgeons should understand the immunobiology of nerve repair and regeneration. In this review, potential stem cell usage in facial nerve regeneration procedures is discussed.
    Postępy Higieny i Medycyny Doświadczalnej (Advances in Hygiene and Experimental Medicine) 09/2015; 69:996-1002. · 0.57 Impact Factor
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    • "MSCs extracted from irradiated pig mandibles were found to keep their proliferative and differentiation abilities even after high radiation doses [14]. While the preclinical data seem promising, very few patient data are available to date: Only one case report using bone marrow aspirates containing a mixture of MSCs and hematopoietic stem cells reported improved bone regeneration after osteoradionecrosis of the maxilla and mandible [77]. "
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    ABSTRACT: Mesenchymal stem cells (MSCs) have been isolated from various organ sites including bone marrow, skin, vascular and adipose tissues and form a heterogeneous population of multipotent stromal cells. They have been shown to exhibit a relative radiation resistance and retain their stem cell properties even after high doses of ionizing radiation. The regenerative potential of MSCs has been widely studied in the context of ischemic or mechanical forms of tissue damage, and these stem cells may also constitute a powerful means of treating tissue lesions caused by ionizing radiation, either after accidental exposure to radioactivity or as a side effect of clinical radiotherapy. Animal studies and early clinical experiences suggest a role for MSCs in the regeneration of these tissue lesions both by differentiating into functional parenchymal cells and by creating a nurturing microenvironment for other cells. Here, we review the published data on the regenerative properties of MSCs in the context of organ-specific radiation damage. Potential mechanisms and clinical applications are outlined, and problems and challenges of MSC-based treatments for radiation injuries in the clinic are summarized. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Cancer letters 07/2015; 366(2). DOI:10.1016/j.canlet.2015.06.012 · 5.62 Impact Factor
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    • "This result slightly differs from those achieved in our previous study [34], in which autologous fat was used as source of mesenchymal stem cell and grafted within irradiated area, inducing clinical benefit that appeared to be linked to the improvement of vascular network and disappearance of necrotic area. Additional results demonstrating the potency of BMSCs therapy in irradiated tissues were recently reported [35] describing a case of regenerative reconstruction of a terminal stage of osteoradionecrosis with BMSCs and progenitor cells. Another explanation that stands for the short effect of engrafted BMSCs might be related to the native hypoxic microenvironment of the medullar area target of the bone. "
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    ABSTRACT: We aimed to explore (i) the short-term retention of intramedullary implanted mesenchymal stem cells BMSCs and (ii) their impact on the bone blood flow and metabolism in a rat model of hindlimb irradiation. Three months after 30 Gy irradiation, fourteen animals were referred into 2 groups: a sham-operated group (n = 6) and a treated group (n = 8) in which ¹¹¹In-labelled BMSCs (2 × 10⁶ cells) were injected in irradiated tibias. Bone blood flow and metabolism were assessed by serial (99m)Tc-HDP scintigraphy and 1-wk cell retention by recordings of (99m)Tc/¹¹¹In activities. The amount of intramedullary implanted BMSCs was of 70% at 2 H, 40% at 48 H, and 38% at 168 H. Bone blood flow and bone metabolism were significantly increased during the first week after cell transplantation, but these effects were found to reduce at 2-mo followup. Conclusion. Short-term cell retention produced concomitant enhancement in irradiated bone blood flow and metabolism.
    BioMed Research International 08/2011; 2011:560257. DOI:10.1155/2011/560257 · 2.71 Impact Factor
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