Although isolated reports of hard-tissue reconstruction in the cranio-maxillofacial skeleton exist, multipatient case series are lacking. This study aimed to review the experience with 13 consecutive cases of cranio-maxillofacial hard-tissue defects at four anatomically different sites, namely frontal sinus (3 cases), cranial bone (5 cases), mandible (3 cases), and nasal septum (2 cases). Autologous adipose tissue was harvested from the anterior abdominal wall, and adipose-derived stem cells were cultured, expanded, and then seeded onto resorbable scaffold materials for subsequent reimplantation into hard-tissue defects. The defects were reconstructed with either bioactive glass or β-tricalcium phosphate scaffolds seeded with adipose-derived stem cells (ASCs), and in some cases with the addition of recombinant human bone morphogenetic protein-2. Production and use of ASCs were done according to good manufacturing practice guidelines. Follow-up time ranged from 12 to 52 months. Successful integration of the construct to the surrounding skeleton was noted in 10 of the 13 cases. Two cranial defect cases in which nonrigid resorbable containment meshes were used sustained bone resorption to the point that they required the procedure to be redone. One septal perforation case failed outright at 1 year because of the postsurgical resumption of the patient's uncontrolled nasal picking habit.

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IntroductionAdipose tissue is an attractive and abundant source of multipotent stem cells. Human adipose stem cells (ASCs) have shown to have therapeutic relevancy in diverse clinical applications. Nevertheless, expansion of ASCs is often necessary before performing clinical studies. Standard in vitro cell-culture techniques use animal-derived reagents that should be avoided in clinical use because of safety issues. Therefore, xeno- and serum-free (XF/SF) reagents are highly desirable for enhancing the safety and quality of the transplanted ASCs.MethodsIn the current study, animal component-free isolation and cell-expansion protocols were developed for ASCs. StemPro MSC SFM XF medium with either CELLstart™ CTS™ coating or Coating Matrix Kit were tested for their ability to support XF/SF growth. Basic stem-cell characteristics such as immunophenotype (CD3, CD11a, CD14, CD19, CD34, CD45RO, CD54, CD73, CD80, CD86, CD90, CD105, HLA-DR), proliferation, and differentiation potential were assessed in XF/SF conditions and compared with human serum (HS) or traditionally used fetal bovine serum (FBS) cultures.ResultsASCs cultured in XF/SF conditions had significantly higher proliferation rates compared with HS/FBS cultures. Characteristic immunophenotypes of ASCs were maintained in every condition; however, cells expanded in XF/SF conditions showed significantly lower expression of CD54 (intercellular adhesion molecule 1, ICAM-1) at low passage number. Further, multilineage differentiation potential of ASCs was maintained in every culture condition.ConclusionsOur findings demonstrated that the novel XF/SF conditions maintained the basic stem cell features of ASCs and the animal-free workflow followed in this study has great potential in clinical cell therapies.

Adipose stromal/stem cells (ASCs) are an ideal cell type for regenerative medicine applications, as they can easily be harvested from adipose tissue in large quantities. ASCs have excellent proliferation, differentiation, and immunoregulatory capacities that have been demonstrated in numerous studies. Great interest and investment have been placed in efforts to exploit the allogeneic use and immunomodulatory and anti-inflammatory effects of ASCs. However, bridging the gap betweenin vitroandin vivostudies and moving into clinical practice remain a challenge. For the clinical translation of ASCs, several issues must be considered, including how to characterise such a heterogenic cell population and how to ensure their safety and efficacy. This review explores the different phases ofin vitroand preclinical ASC characterisation and describes the development of appropriate potency assays. In addition, good manufacturing practice requirements are discussed, and cell-based medicinal products holding marketing authorisation in the European Union are reviewed. Moreover, the current status of clinical trials applying ASCs and the patent landscape in the field of ASC research are presented. Overall, this review highlights the applicability of ASCs for clinical cell therapies and discusses their potential.