Clinical Trial of Fat Grafts Supplemented With Adipose-derived Regenerative Cells

Randomized Controlled Clinical Trial of Fat Grafts Supplemented With Adipose-derived Regenerative Cells for Facial Soft Tissue Augmentation in Patients With Craniofacial Microsomia.

Although first reports of the clinical use of adipose-derived regenerative cells (ADRC) suggest that this approach may be feasible and effective for soft tissue augmentation, there is a lack of randomized, controlled clinical trials in the literature. Hence, this study aimed to investigate whether a novel protocol for isolation of ADRC and their use in combination with fat tissue improve the long-term retention of the grafts in patients with craniofacial microsomia.

Study Overview

• Status: Completed
• Conditions: Craniofacial Microsomia
• Intervention / Treatment: Procedure: Supplementation of ADRC; Procedure: Without supplementation of ADRC

Detailed Description

To overcome problems associated with fat grafting, such as unpredictable clinical results and a low rate of graft survival, many innovative efforts and refinements of surgical techniques have been reported. For example, condensation of living tissue and removal of unnecessary components have been performed by centrifugation, filtration or gravity sedimentation; external mechanical force has been used to expand the recipient tissue as well as the overlying skin envelope; and a recent experimental study has suggested that repeated local injections of erythropoietin might enhance retention of grafted fat.

Based on the finding that aspirated fat tissue contains a much smaller number of adipose-derived regenerative cells (ADRC) compared with intact tissue and that these cells play pivotal roles in the adipose tissue remodeling after lipoinjection, the supplementation of fat grafts with stromal vascular fraction isolated from adipose portion of liposuction aspirates has been proposed as a method to compensate its relative deficiency of ADRC.

In the literature, there are at least three experimental studies demonstrating that supplementation of adipose progenitor cells enhances the volume or weight of surviving adipose tissue, and first reports of the clinical use of ADRC suggest that this approach may be feasible and effective for soft tissue augmentation.

However, since these studies represent level of evidence IV, which correspond to the publication of case series, there is a lack of randomized, controlled clinical trials comparing this method to current standard techniques.

Hence, this study aimed to fill this gap by investigating whether a novel protocol for isolation of ADRC and their use in combination with fat tissue improve the long-term retention of the grafts in patients with craniofacial microsomia.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 01246000
      • Division of Plastic and Reconstructive Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Unilateral craniofacial microsomia
• 10 to 35 years old
• Phenotype (M0, M1 or M2) and (S1 or S2) according to the OMENS-PLUS classification

Exclusion Criteria:

• Previous soft tissue surgery
• Absence of fat donor site

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: With supplementation of ADRC; Fat graft with supplementation of ADRC	Procedure: Supplementation of ADRC; Isolation of ADRC from half of the aspirated fat and supplementation of the fat grafts with these cells; Other Names: Cell-assisted lipotransfer
Active Comparator: Without supplementation of ADRC; Fat grafts without supplementation of ADRC	Procedure: Without supplementation of ADRC; Standard fat graft preparation; Other Names: Structural fat grafting

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Graft volume retention	Graft volume retention evaluated by CT-scan performed at the preoperative period and at 6-months postoperative	6 months postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of viable cells before and after the supplementation of the grafts	Number of viable cells in adipose tissue evaluated by trypan blue method immediately after surgery	immediate postoperative

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Investigators: Principal Investigator: Daniela Y Tanikawa, MD, Division of Plastic and Reconstructive Surgery, University of São Paulo School of Medicine

Publications and helpful links

General Publications

• Yoshimura K, Sato K, Aoi N, Kurita M, Hirohi T, Harii K. Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adipose-derived stem/stromal cells. Aesthetic Plast Surg. 2008 Jan;32(1):48-55; discussion 56-7. doi: 10.1007/s00266-007-9019-4. Epub 2007 Sep 1.
• Yoshimura K, Sato K, Aoi N, Kurita M, Inoue K, Suga H, Eto H, Kato H, Hirohi T, Harii K. Cell-assisted lipotransfer for facial lipoatrophy: efficacy of clinical use of adipose-derived stem cells. Dermatol Surg. 2008 Sep;34(9):1178-85. doi: 10.1111/j.1524-4725.2008.34256.x. Epub 2008 May 29.
• Yoshimura K, Asano Y, Aoi N, Kurita M, Oshima Y, Sato K, Inoue K, Suga H, Eto H, Kato H, Harii K. Progenitor-enriched adipose tissue transplantation as rescue for breast implant complications. Breast J. 2010 Mar-Apr;16(2):169-75. doi: 10.1111/j.1524-4741.2009.00873.x. Epub 2009 Nov 12.
• Yoshimura K, Eto H, Kato H, Doi K, Aoi N. In vivo manipulation of stem cells for adipose tissue repair/reconstruction. Regen Med. 2011 Nov;6(6 Suppl):33-41. doi: 10.2217/rme.11.62.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: August 22, 2012
• First Submitted That Met QC Criteria: August 27, 2012
• First Posted (Estimate): August 28, 2012

Study Record Updates

• Last Update Posted (Estimate): August 28, 2012
• Last Update Submitted That Met QC Criteria: August 27, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Cell therapy; Adipose-derived regenerative cells; Autologous fat transfer; Tissue engineering; Craniofacial microsomia
• Additional Relevant MeSH Terms: Pathologic Processes; Congenital Abnormalities; Musculoskeletal Diseases; Bone Diseases; Fetal Diseases; Pregnancy Complications; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Growth Disorders; Bone Diseases, Developmental; Mandibulofacial Dysostosis; Craniofacial Dysostosis; Dysostoses; Fetal Growth Retardation; Goldenhar Syndrome
• Other Study ID Numbers: 1069/08; CEPID-FAPESP 98/14254-2 (Other Grant/Funding Number: CEPID-FAPESP 98/14254-2)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No