Implantation of Stromal Vascular Fraction Progenitors at Bone Fracture Sites: From a Rat Model to a First-in-Man Study

Saxer, Franziska; Scherberich, Arnaud; Todorov, Atanas; Studer, Patrick; Miot, Sylvie; Schreiner, Simone; Güven, Sinan; Tchang, Laurent A.; Haug, Martin; Heberer, Michael; Schaefer, Dirk J.; Rikli, Daniel; Martín, Iván; Jakob, Marcel

doi:10.1002/stem.2478

Cited by 61 publications

(62 citation statements)

References 41 publications

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“…Interestingly, subsequent immunohistochemical analyses of biopsy specimens also revealed a higher quantity and quality/maturity of blood vessels in the areas of active bone formation (Farre‐Guasch et al., ). Similar results were observed in a phase I clinical study of orthopaedic fracture treatment with A‐SVF (Saxer et al., ). Indeed, previous studies have demonstrated the angiogenic and vasculogenic potential of A‐SVF, attributed to the presence of ECs and perivascular cells (Jin, Chae, Son, & Kim, ; Zakhari, Zabonick, Gettler, & Williams, ).…”

Section: Discussionsupporting

confidence: 87%

Cell therapy for orofacial bone regeneration: A systematic review and meta‐analysis

Shanbhag

Suliman

Pandis

et al. 2019

J Clinic Periodontology

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Aim The objective of the present review was to answer the focused question: what is the effect of cell therapy in terms of orofacial bone regeneration compared to grafting with only biomaterial scaffolds and/or autogenous bone? Methods Electronic databases were searched for relevant controlled clinical and pre‐clinical (large‐animal) studies. Separate meta‐analyses of quantitative data regarding histological or radiographic new bone formation were performed. Results Forty‐seven eligible clinical and 57 pre‐clinical studies were included. Clinical studies were categorized based on the use of “minimally manipulated” whole tissues (e.g., bone marrow) or ex vivo expanded cells from “uncommitted” (bone marrow, adipose tissue) or “committed” sources (periosteum, bone). Based on limited and heterogeneous clinical evidence, implantation of cells (mostly whole bone marrow), in combination with biomaterial scaffolds results in bone regeneration which is (a) superior compared to implantation of scaffolds alone in sinus and horizontal ridge augmentation, and (b) comparable to autogenous bone in alveolar cleft repair. Conclusions Although current evidence points to the benefits of cell therapy in certain clinical indications, it is unclear whether the use of ex vivo expanded cells, either uncommitted or committed, is superior to whole tissue fractions in terms of bone regeneration. The relatively larger effect sizes in favour of cell therapy observed in pre‐clinical studies are diminished in clinical trials. Future controlled studies should include cost‐effectiveness analyses to guide clinical decision‐making.

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Section: Discussionsupporting

confidence: 87%

Cell therapy for orofacial bone regeneration: A systematic review and meta‐analysis

Shanbhag

Suliman

Pandis

et al. 2019

J Clinic Periodontology

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“…Another study has showed that implantation of human SVF cells into bone fracture sites of nude rats enhances osteogenic ability. This study also showed spontaneous bone tissue and vessel formation within a fracture microenvironment with SVF . In these studies, local injection of SVF cells was applied, whereas systemic transplantation of noncultured SVF cells was applied in the current study.…”

Section: Discussionmentioning

confidence: 94%

Transplantation of Noncultured Stromal Vascular Fraction Cells of Adipose Tissue Ameliorates Osteonecrosis of the Jaw–Like Lesions in Mice

Kuroshima

Sasaki

Nakajima

et al. 2017

Journal of Bone and Mineral Research

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The precise pathoetiology and effective treatment strategies for bisphosphonate-related osteonecrosis of the jaw (BRONJ) remain unknown. Transplantation of noncultured stromal vascular fraction (SVF) cells has been shown to be a useful method for regenerative medicine in place of stem cell therapy. This study investigated the effects of noncultured SVF transplantation on tooth extraction socket healing in mice. Both chemotherapeutic/bisphosphonate combination therapy for 7 weeks and tooth extraction of maxillary first molars at 3 weeks after drug administration were performed using female C57BL/6J mice. Osseous and soft tissue wound healing were validated at 4 weeks postextraction using gross wound healing and histomorphometry. Here, we created a new animal model of high-prevalence ONJ-like lesions that mimic human progression, because human ONJ mainly occurs in female patients taking both chemotherapeutic and bisphosphonate following tooth extraction. Moreover, mice with chemotherapeutic and bisphosphonate combination therapy for 5 weeks received SVF transplantation just after tooth extraction at 3 weeks post-drug administration. Euthanasia was performed at 2 weeks postextraction to assess the transplantation effects on wound healing using gross wound healing, histomorphometry, immunohistomorphometry, quantitative real-time polymerase chain reaction, and microcomputed tomography. We showed that systemic transplantation of noncultured SVF cells ameliorates ONJ-like lesions by improving both osseous and soft tissue healing of tooth extraction sockets. SVF therapy significantly increased blood vessels and the ratio of M2/M1 macrophages. In addition, SVF transplantation reduced the increases in tartrate-resistant acid phosphatase-positive (TRAP þ ) mononuclear cells (MNCs) and nonattached osteoclasts from the bone surface, which were significantly detected in the connective tissue of tooth extraction sockets and bone marrow by chemotherapeutic/bisphosphonate combination therapy. Our findings suggest that transplantation of noncultured SVF cells is a suitable treatment for BRONJ. Abnormal TRAP þ MNCs and nonattached osteoclasts in systemic and local environments may contribute to the development of BRONJ.

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“…Almost all organ system have been implicated in adipose‐derived cell therapy. The indication for treatment in the included studies was (in order count) soft tissue , gastrointestinal , musculoskeletal , rheumatological , ulcer/ischemic limb , urogenital , cardiac , neurological , immunological , pulmonary , and ophthalmological (Fig. A).…”

Section: Resultsmentioning

confidence: 99%

“…Almost all organ system have been implicated in adipose-derived cell therapy. The indication for treatment in the included studies was (in order count) soft tissue www.StemCellsTM.com [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35], gastrointestinal [8,[36][37][38][39][40][41][42][43][44][45][46][47][48], musculoskeletal [49][50][51][52][53][54][55][56][57][58], rheumatological [59][60][61][62][63], ulcer/ischemic limb [64][65][66][67], urogen...…”

Section: Description Of Included Studiesmentioning

confidence: 99%

Concise Review: A Safety Assessment of Adipose-Derived Cell Therapy in Clinical Trials: A Systematic Review of Reported Adverse Events

Toyserkani

Jørgensen

Tabatabaeifar

et al. 2017

Stem Cells Translational Medicine

107

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The popularity of adipose‐derived cell therapy has increased over the last decade, and the number of studies published annually is growing. However, concerns regarding safety in the setting of previous malignancy or the use of allogeneic cells have been raised. We therefore aimed to systematically review all clinical studies using adipose‐derived cell therapy to identify reported adverse events with a special focus on risk of thromboembolic, immunological, and oncological safety concerns. Our systematic search resulted in 70 included studies involving more than 1,400 patients that were treated with adipose‐derived cell therapy. Safety assessment method was not described in 32 of the included studies. For studies involving systemic or cardiac administration, one case of pulmonary thromboembolism and cases of both myocardial and cerebral infarctions were described. In the setting of allogeneic cell therapy studies, where the production of specific antibodies toward donor cells was examined, it was noted that 19%–34% of patients develop antibodies, but the consequence of this is unknown. With regard to oncological safety, only one case of breast cancer recurrence was identified out of 121 patients. Adipose‐derived cell therapy has so far shown a favorable safety profile, but safety assessment description has, in general, been of poor quality, and only adverse events that are looked for will be found. We encourage future studies to maintain a strong focus on the safety profile of cell therapy, so its safeness can be confirmed. stem cells translational medicine 2017;6:1786–1794

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Implantation of Stromal Vascular Fraction Progenitors at Bone Fracture Sites: From a Rat Model to a First-in-Man Study

Cited by 61 publications

References 41 publications

Cell therapy for orofacial bone regeneration: A systematic review and meta‐analysis

Cell therapy for orofacial bone regeneration: A systematic review and meta‐analysis

Transplantation of Noncultured Stromal Vascular Fraction Cells of Adipose Tissue Ameliorates Osteonecrosis of the Jaw–Like Lesions in Mice

Concise Review: A Safety Assessment of Adipose-Derived Cell Therapy in Clinical Trials: A Systematic Review of Reported Adverse Events

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