Autologous Bone Marrow-Derived Mononuclear Cell Transplantation in Accelerating Tissue Expansion and Skin Regeneration

Phase 1/2 Study of Autologous Bone Marrow-Derived Mononuclear Cell Transplantation in Accelerating Soft Tissue Expansion

The purpose of this study is to evaluating whether autologous bone marrow mononuclear cells transplantation is safe and/or effective to accelerating skin regeneration and soft tissue expansion.

Study Overview

• Status: Unknown
• Conditions: Tissue Expansion;; Skin Regeneration;; Reconstruction;; Bone Marrow Mononuclear Cells
• Intervention / Treatment: Procedure: Autologous bone marrow mononuclear cells; Procedure: Placebo

Detailed Description

Reconstruction of large scale skin defect is a challenge to clinical surgeons. Soft tissue expansion has won wide attention in recent years as it promotes skin regeneration with perfectly matched tissue. However, some patients with poor skin regenerative ability would suffer from skin flap over-thinned and even necrosis under the continuous stretching by silicone expander. Although, on some occasions, decelerating the expander inflation process could reduce the incidence of necrosis, this prolonged therapy circle is to be accompanied with increased complications, including infection and expander rupture, as well as the increased economic expenses by the longer hospitalization. This study is to observe the effects of autologous bone marrow mononuclear cell transplantation on accelerating skin regeneration and promoting tissue expansion process.

Patients aged between 18 to 60 years old who appear with deteriorated expanded skin will be enrolled and randomized into two groups, named as the experimental group and the control group. Patients from the experimental group will have a bone marrow aspiration and intradermal mononuclear cells transplantation. On the other side, Patients from the control group will have saline injection.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200011
      • Recruiting
      • Shanghai Ninth People's Hospital, Affliated to Shanghai Jiao Tong University School of Medicine
      • Contact: Qingfeng Li, MD, PhD; Phone Number: 0086 21 63089567; Email: liqfliqf@yahoo.com.cn
      • Contact: Shuangbai Zhou, MD; Phone Number: 0086 13482514585; Email: shuangbaizhou@gmail.com
      • Principal Investigator: Qingfeng Li, MD, PhD
      • Sub-Investigator: Shuangbai Zhou, MD
      • Sub-Investigator: Tao Zan, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age of 18 to 60 years;
• Expanding skin donor site at the face, neck, anterior chest wall, abdominal wall or back;
• Implanted silicone expander of 80 to 600 ml in size;
• History of deterioration in the expanded skin texture that did not improve after the inflation procedure was suspended for more than 2 weeks;
• Persistent high level of expander internal pressure;
• Need for further skin expansion;

Exclusion Criteria:

• Not fit for soft tissue expansion treatment;
• Evidence of infection, ischemia, ulcer or other pathological changes within the targeting area which defined as not suitable for expansion; or history of delayed healing, radiational therapy;
• Significant renal, cardiovascular, hepatic and psychiatric diseases;
• Significant medical diseases or infection (including but not limited to the carrier of hepatitis B virus or HIV)
• BMI >30;
• History of any hematological disease, including leukopenia , thrombocytopenia, or thrombocytosis;
• History of allogenic bone marrow transplantation;
• Long history of smoking;
• Evidence of malignant diseases or unwillingness to participate.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous bone marrow mononuclear cells; Patients received autologous MNC transplantation. Bone marrow aspirates are harvested from the anterior iliac crest of the patients under general or local anesthesia. MNCs are isolated by density gradient centrifugation. The cell suspension was adjusted to a final volume of 6-20 ml with saline. The cell suspension was injected into expanded skin intradermally via a 27-gauge needle (approximately 0.5-1×10^6 cells/cm2).	Procedure: Autologous bone marrow mononuclear cells; Autologous bone marrow-derived mononuclear cells, after isolated by density gradient centrifugation from bone marrow aspiration and resuspended in saline, will be transplanted subcutaneously to expanded skin. The number of infused cells will be 1x10e6/cm2.
Placebo Comparator: Saline; Patient has intradermally and subcutaneously injection of saline.	Procedure: Placebo; Patients will have mimical bone marrow aspiration under local anesthesia following with saline injection to expanded skin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurence of major adverse events	Including expanded flap ischaemia, necrosis, fluidify, infection, and all other adverse events	Up to approximately 24 months after study start
To measure inflation volume of the silicone expander		baseline, 4 weeks and 8 weeks post treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
To measure the size of expanded flap	baseline and 8 weeks post treatment
To measure the texture of expanded flap	4 weeks and 8 weeks post treatment
To measure expanded skin thickness by ultrasound scanning	baseline, 4 weeks and 8 weeks post treatment
Laboratory examinations including routine blood test, liver function and renal function	baseline and 8 weeks post stem cell transplantation

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Investigators: Study Director: Qingfeng Li, MD, PhD, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine

Publications and helpful links

General Publications

• Zhou SB, Zhang GY, Xie Y, Zan T, Gan YK, Yao CA, Chiang CA, Wang J, Liu K, Li H, Zhou J, Yang M, Gu B, Xie F, Pu LQ, Magee WP 3rd, Li QF. Autologous Stem Cell Transplantation Promotes Mechanical Stretch Induced Skin Regeneration: A Randomized Phase I/II Clinical Trial. EBioMedicine. 2016 Nov;13:356-364. doi: 10.1016/j.ebiom.2016.09.031. Epub 2016 Oct 1.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): October 1, 2013
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: September 2, 2010
• First Submitted That Met QC Criteria: September 24, 2010
• First Posted (Estimate): September 27, 2010

Study Record Updates

• Last Update Posted (Estimate): April 22, 2014
• Last Update Submitted That Met QC Criteria: April 21, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: 30730092