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American Association of Plastic Surgeons
19. Therapeutic angiogenesis for ischemic tissue by autologous transplantation of adipose-derived adult stem cells.
Gino Rigotti, M.D.1, Alessandra Marchi, M.D.1, Mirco Gallič, Ph.D.2, Guido Baroni3, Donatella Benati4, Andrea Sbarbati5.
1Azienda Ospedaliera Verona, Verona, Italy, 2Istituto di Anatomia Umana Universitā di Verona, Verona, Italy, 3Dipartimento di Bioingenieria-Politecnico di Milano, Milano, Italy, 4Istituto di Anatomia Umana Universitā di Verona, Verona, Italy, 5Istituto di Anatomia Umana Universitā di Verona, Verona, Italy.

Purpose
There are evidences that stem cells contribute to restore tissue vascularization and organ function. Significant clinical results were obtained with bone marrow stem cells after ischaemic events in limbs and myocardium. Human adipose tissue was proved to represent a rich source of mesenchymal stem cells (AMSCs) exhibiting multilineage potential and featuring secretion of angiogenic and antiapoptotic factors in animals.
Methods
Twenty consenting patients exhibiting a previously never described scleroderma-like chronic microangiopathy after radiotherapy were treated with transplants of lipoaspirate containing AMSCs within their natural scaffold; it was directly injected into the radio-damaged areas. A computer-based procedure was used to plan the optimal patterns of lipoaspirate injection. Ultrastructural studies were performed on the lipoaspirate and on tissue samples from the radio-damaged areas, before transplantation and after 1, 2, 4-6 and 12 months.Cytofluorimetric-based examination on lipoaspirate was performed.
The technique for AMSCs purification and injection within their natural scaffold is based on centrifugation. Cells culture is not necessary. Clinical results were evaluated with LENT-SOMA scale.
Results
At cytofluorimetric-based examination, human lipoaspirates resulted to contain at least 1.8x103 AMSCs/cc. Ultrastructural analysis demonstrated that radiation-induced alterations of microcirculation were solved by a newly formed microcirculation after AMSCs transplant, leading to the restitutio ad integrum of the treated tissues.
Significant clinical improvements were constantly observed. In the group of 11 patients with LENT-SOMA scale grade 4 damage, 4 progressed to grade 0; 5 to grade 1 and 2 to grade 2. In the group of 9 patients with grade 3 damage, 5 progressed to grade 0 and 4 to grade 1.
Conclusions
This work is focused on human adipose mesenchimal stem cells, which have been recently found to secrete angiogenic factors in mices but have never been previously used for ischemic tissue neovascularization in humans. The study demonstrates the therapeutic efficacy of AMSCs, for the treatment of radiation-induced damages through a process of replacement of damaged tissue with reconstructed normal tissue. AMSCs procurement is easy and safe. The technique for AMSCs purification and injection within their natural scaffold is simple and low-cost and exhibits the lowest risk of micro-organism contamination.


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