Role of Mesenchymal Stem Cells in Fat Grafting

Lipodystrophy Clinical Trial

Official title:

Potential of Mesenchymal Stem Cell Enriched Adipose Tissue Grafting for Contour Deformities of Face

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02494752
• Other study ID #: 229/RC/KEMU
• Status: Not yet recruiting
• Phase: N/A
• First received: July 4, 2015
• Last updated: July 9, 2015
• Start date: August 2015
• Est. completion date: February 2016

Study information

• Verified date: July 2015
• Source: King Edward Medical University
• Contact: Muhammad M Bashir, F.C.P.S
• Phone: 923336517745
• Email: mmbashir1[@]gmail.com
• Is FDA regulated: No
• Health authority: Pakistan: Institutional Review Board King Edward Medical University
• Study type: Interventional

Clinical Trial Summary

Contour deformity of face causes both functional as well as aesthetic problems for the patient. Fat being an autologous tissue source is considered as an ideal soft-tissue filler because it is abundant, readily available, inexpensive, host compatible, and can be harvested easily and repeatedly. However absorption of grafted fat is a major problem resulting in lack of consistency of final clinical outcome. Adipose tissue derived mesenchymal stem cells have the potential to enhance the viability of the grafted fat and the reliability of the final outcome of surgery. In the current study potential of mesenchymal stem cells will be studied by comparing two groups of patients requiring fat grafting for contour deformities of face. Control group will have fat graft with out enrichment with stem cells whereas experimental group will have their fat graft enriched with mesenchymal stem cells. Comparison will be made regarding viability of grafted fat in two groups.

Description:

Contour deformities of the face requiring soft tissue augmentation often result from conditions such as congenital disorders, acquired diseases, and traumatic and developmental deformities. Significant contour deformity of face causes both functional as well as aesthetic problems for the patient. Conventionally, these problems are treated by allogenic fillers, major flap surgery and fat grafting.1 However; different problems are associated with above mentioned treatment options. For example, allogenic fillers are foreign material that poses not only allergic reactions but also rapid absorption at the site of application. Similarly, flap surgery, in the form of pedicled and free flaps, produces considerable donor site morbidity. In addition, fine- tuning is impossible with flap, and tissue transferred in the form of flap may act as blob.

Autologous fat grafting has gained pervasive acceptance for the management of contour deformities of the face. Fat being an autologous tissue source is considered as an ideal soft-tissue filler because it is abundant, readily available, inexpensive, host compatible, and can be harvested easily and repeatedly.2 Although the practice of fat grafting is not new and it is a safe and natural method of soft-tissue augmentation, the viability and reliability of transplanted fat grafts remains poorly studied. One major concern is the lack of consistency of final clinical outcome, which often requires multiple fat grafting procedures making it expensive. Rate of fat absorption may reach up to 40% to 80%.However, previously published data have failed to produce a cohesive algorithm of the required components for successful, consistent and durable fat transplantation.3 In order to overcome problems associated with fat grafting, other innovative techniques are required.

The role of fat auto-transplantation in plastic surgery has evolved from a controversial technique designed for simple volume augmentation to the foundation for the innovative and burgeoning field of regenerative medicine. This is based on the fact that adipose tissue contains adipocytes and the stromal vascular fraction (SVF) consisting of multiple cell types such as circulating blood cells, fibroblasts, pericytes, endothelial cells, and mesenchymal stem cells (MSCs). Adipocytes account for 20 percent or fewer of the total number of cells in adipose tissue4whereasthere are only 3% MSCs in SVF of adipose tissue.5 Although this percentage is relatively low, this cell type is the main contributor in overall healing process. MSCs derived from adipose tissue (AT-MSCs) have high proliferative potential and ability to differentiate into mesenchymal (adipose, bone, cartilage) and non-mesenchymal (neuron like cells) lineages.6,7,8 AT-MSCs have been shown to enhance angiogenesis, decrease apoptosis and modify the local inflammatory response owing to their immunosuppressive and immunomodulatory properties.9 Therefore, the current study is designed to evaluate the effect of fat grafting and AT-MSCs together on contour deformities of face. By combining traditional fat graft with AT-MSCs, tissue viability and therefore the consistency of graft survival may be improved. In the current model investigators propose that transferred fat may act as a natural scaffold and temporary filler to restore the volume immediately while AT-MSCs will start participating in multiple parameters of tissue regeneration. This model supports the "host replacement theory" that has been put forward to describe how fat grafts survive after they are transplanted.10 Due to problems associated with fat grafting alone, it is desirable to solve such issues by using innovating techniques. In the current study investigators propose the novel idea of enrichment of conventional fat graft with ex-vivo expanded AT-MSCs to enhance the viability of the grafted fat and the reliability of the final outcome of surgery. Recent animal studies have suggested that AT-MSCs that have been expanded before administration could help preserve grafted fat and improve outcomes.11 Thus rationale of current study is to compare the outcome of conventional fat grafting with stem cell enriched fat grafting for contour deformities of face. If enrichment of fat graft with AT-MSCs can decrease its absorption rate, this innovative strategy can make fat transfer a reliable option for soft tissue augmentation. This can definitely improve final clinical outcome at lesser cost and reduced donor site morbidity

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 60 Years

Eligibility

Inclusion Criteria:

• Patients with congenital and acquired contour deformities of face requiring soft tissue augmentation .

• Must be 16-60 years of age

• Must be American Society of Anesthesiology (ASA) class 1 and 2

Exclusion Criteria:

• Patients with contour deformities in which skin is adherent to facial skeleton

• Contour deformities underlying skin grafted areas of face

• Abdominal skin pinch thickness less than 3 inch

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Connective Tissue Diseases
• Craniofacial Microsomia
• Goldenhar Syndrome
• Lipodystrophy
• Mixed Connective Tissue Disease
• Romberg's Disease

Intervention

Procedure:
• Fat graft enriched with ex vivo expanded stem cells
Fat graft will be enriched with ex vivo expanded stem cells
• Fat graft not enriched with ex vivo expanded stem cells
Fat graft will not be enriched with ex vivo expanded stem cells

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
King Edward Medical University

References & Publications (13)

Baer PC, Geiger H. Adipose-derived mesenchymal stromal/stem cells: tissue localization, characterization, and heterogeneity. Stem Cells Int. 2012;2012:812693. doi: 10.1155/2012/812693. Epub 2012 Apr 12. — View Citation

Bollero D, Pozza S, Gangemi EN, De Marchi A, Ganem J, A M el K, Faletti C, Stella M. Contrast-enhanced ultrasonography evaluation after autologous fat grafting in scar revision. G Chir. 2014 Nov-Dec;35(11-12):266-73. — View Citation

Brown SA, Levi B, Lequeux C, Wong VW, Mojallal A, Longaker MT. Basic science review on adipose tissue for clinicians. Plast Reconstr Surg. 2010 Dec;126(6):1936-46. doi: 10.1097/PRS.0b013e3181f44790. Review. Erratum in: Plast Reconstr Surg. 2011 Feb;127(2):1025. Lequex, Charlotte [corrected to Lequeux, Charlotte]. — View Citation

Bucky LP, Kanchwala SK. The role of autologous fat and alternative fillers in the aging face. Plast Reconstr Surg. 2007 Nov;120(6 Suppl):89S-97S. — View Citation

Cheong YW, Lo LJ. Facial asymmetry: etiology, evaluation, and management. Chang Gung Med J. 2011 Jul-Aug;34(4):341-51. Review. — View Citation

Choudhery MS, Badowski M, Muise A, Harris DT. Comparison of human mesenchymal stem cells derived from adipose and cord tissue. Cytotherapy. 2013 Mar;15(3):330-43. doi: 10.1016/j.jcyt.2012.11.010. Epub 2013 Jan 11. — View Citation

Choudhery MS, Badowski M, Muise A, Pierce J, Harris DT. Cryopreservation of whole adipose tissue for future use in regenerative medicine. J Surg Res. 2014 Mar;187(1):24-35. doi: 10.1016/j.jss.2013.09.027. Epub 2013 Oct 8. — View Citation

Choudhery MS, Badowski M, Muise A, Pierce J, Harris DT. Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation. J Transl Med. 2014 Jan 7;12:8. doi: 10.1186/1479-5876-12-8. — View Citation

Eto H, Kato H, Suga H, Aoi N, Doi K, Kuno S, Yoshimura K. The fate of adipocytes after nonvascularized fat grafting: evidence of early death and replacement of adipocytes. Plast Reconstr Surg. 2012 May;129(5):1081-92. doi: 10.1097/PRS.0b013e31824a2b19. — View Citation

Gir P, Brown SA, Oni G, Kashefi N, Mojallal A, Rohrich RJ. Fat grafting: evidence-based review on autologous fat harvesting, processing, reinjection, and storage. Plast Reconstr Surg. 2012 Jul;130(1):249-58. doi: 10.1097/PRS.0b013e318254b4d3. Review. — View Citation

Gir P, Oni G, Brown SA, Mojallal A, Rohrich RJ. Human adipose stem cells: current clinical applications. Plast Reconstr Surg. 2012 Jun;129(6):1277-90. doi: 10.1097/PRS.0b013e31824ecae6. Review. — View Citation

Kølle SF, Fischer-Nielsen A, Mathiasen AB, Elberg JJ, Oliveri RS, Glovinski PV, Kastrup J, Kirchhoff M, Rasmussen BS, Talman ML, Thomsen C, Dickmeiss E, Drzewiecki KT. Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival: a randomised placebo-controlled trial. Lancet. 2013 Sep 28;382(9898):1113-20. doi: 10.1016/S0140-6736(13)61410-5. — View Citation

Tiryaki T, Findikli N, Tiryaki D. Staged stem cell-enriched tissue (SET) injections for soft tissue augmentation in hostile recipient areas: a preliminary report. Aesthetic Plast Surg. 2011 Dec;35(6):965-71. doi: 10.1007/s00266-011-9716-x. Epub 2011 Apr 13. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in thickness of subcutaneous tissue	Objective assessment will be made by doing baseline B mode colour Doppler ultrasonography of the treated area.The operator blinded to the group allocation will measure the thickness of the subcutaneous tissue (in millimeters) in the treated area during the baseline examination with ultrasound B-mode. In order to have a reproducible measurement in subsequent examinations, the operator will look for and note down precise anatomical landmarks or, in case of large areas, will mark the points with an indelible marker, saving a digital image for future reference. Patients will again under go ultrasonography of the treated area at 24 weeks post treatment. During this repeat ultra sonography same operator will again measure the subcutaneous thickness of the treated in millimeters. The difference in two measurements will be noted down as residual volume. Means of residual volumes in two groups will be compared.	24 weeks	No
Secondary	Change from base line in post operative appearance	Subjective assessment will be done by taking photographs preoperatively and 24 weeks post treatment months under standard conditions of light, distance, views and camera make. Two plastic surgeons blinded to group allocation will rate post operative appearance as satisfactory/unsatisfactory by comparing pre and post operative photographs.	24 weeks	No