10/02/2015

Background: The Regenerative property of fat grafting has been described. However, it is not clear whether the clinical results are attributable to the stem cells or are linked to other components of the adipose tissue. This work is aimed at analysis of the histologic and ultrastructural changes of aged facial skin after injection of fat graft added in addition to its stromal vascular fraction, obtained by centrifugation, and to compare the results with those obtained by the injection of expanded adipose-derived mesenchymal stem cells.

Methods: This study was performed in six consecutive patients who were candidates for face lift and whose ages ranged between 45 and 65 years. The patients underwent stampling of fat by liposuction from the abdominal region. The injection of fat and its stromal vascular fraction or expanded mesenchymal stem cells was performed in the preauricular areas. Fragments of skin were removed before and 3 months after each treatment and analyzed by optical and electron microscopy.

Results: After treatment with the autologous lipidic component and stromal vascular fraction, the skin showed a decrease in elastic fiber network (elastosis) and the appearance of new oxytalan elastic fibers in papillary dermis. The ultrastructural examination showed a modifed tridimensional architecuture of the reticular dermis and the presence of a richer microvascular bed. Results following treatment with expanded mesenchymal stem cells did not differ significantly from what is generated by the fat graft and its stromal vascular fraction.

Conclusion: This study demonstrates that treatment with either fat and stromal vascular fraction or expanded mesenchymal stem cells modifies the pattern of the dermis, representing a skin rejuvenation effect.

Gino Rigotti • Alessandra Marchi • Paolo Stringhini •
Guido Baroni • Mirco Galie` • Anna Maria Molino •
Anna Mercanti • Rocco Micciolo • Andrea Sbarbati

Abstract

This study compares the incidence of local and regional recurrence of breast cancer between two contiguous time windows in a homogeneous population of 137 patients who underwent fat tissue transplant after modified radical mastectomy. Median follow-up time was 7.6 years and the follow-up period was divided into two contiguous time windows, the first starting at the date of the radical mastectomy and ending at the first lipoaspirate grafting session and the second beginning at the time of the first lipoaspirate grafting session and ending at the end of the total follow-up time. Although this study did not employ an independent control group, the incidence of local recurrence of breast cancer was found to be comparable between the two periods and in line with data from similar patient populations enrolled in large multicenter clinical trials and who did not undergo postsurgical fat tissue grafting. Statistical comparison of disease-free survival curves revealed no significant differences in relapse rate between the two patient subgroups before fat grafting and after fat grafting. Although further confirmation is needed from multicenter randomized clinical trials, our results support the hypothesis that autologous lipoaspirate transplant combines striking regenerative properties with no or marginal effects on the probability of post-mastectomy locoregional recurrence of breast cancer.

Keywords

Autologous fat grafting

Breast cancer

Adipose-derived stem cells

Reconstructive surgery

Tissue regeneration

Gino Rigotti, M.D.
Alessandra Marchi, M.D.
Mirco Galie` , Ph.D.
Guido Baroni, Ph.D.
Donatella Benati, Ph.D.
Mauro Krampera, M.D.
Annalisa Pasini, Ph.D.
Andrea Sbarbati, M.D.

Background:

There is evidence that stem cells contribute to the restoration of tissue vascularization and organ function. The objective of this study was to assess the presence of adipose-derived adult stem cells left in their natural scaffold in the purified lipoaspirate and to assess the clinical effectiveness of lipoaspirate transplantation in the treatment of radiation side effects.

Methods:

This study was designed beginning with surgical procedures in 2002 and envisaging a continuous patient follow-up to 31 months. Twenty consecutive patients undergoing therapy for side effects of radiation treatment with severe symptoms or irreversible function damage (LENT-SOMA scale grade 3 and 4) were enrolled. Purified autologous lipoaspirates (60 to 120 cc) taken from a healthy donor site were administered by repeated low-invasive computer-assisted injection. Therapy outcomes were assessed by symptoms classification according to the LENT-SOMA scale, cytofluorimetric characterization, and ultrastructural evaluation of targeted tissue.

Results:

In the isolated stromal vascular fraction of 2 cc of human lipoaspirate, cells with mesenchymal stem cell physical properties and immunophenotype were in average 1.07
0.5 percent (n  4), with a clonogenic fraction of 0.139 percent. At least 1.02103 colony-forming units–fibroblast were present in each lipoaspirate. Ultrastructure of target tissue systematically exhibited progressive regeneration, including neovessel formation and improved hydration. Clinical outcomes led to a systematic improvement or remission of symptoms in all evaluated patients, including otherwise untreatable patients exhibiting initial irreversible functional damage.

Conclusions:

This surgical procedure is a low-invasive therapeutic approach for resolving the late side effects of radiotherapy.According to the proposed hypothesis of the ischemic nature of radiolesions, treatment with lipoaspirate transplantation is potentially extended to other forms of microan giopathies.

Dr Gino Rigotti

Dr Alessandra Marchi

Dr Andrea Sbarbati

Abstract

It is likely that in the future, the past decade in the history of plastic surgery will be remembered for the introduction of reconstructive therapies based on the use of stem cells. Of the variety of different approaches that have been proposed, those that have been most widely used in recent years, and which therefore seem most promising for the future, are those using adipose-derived mesenchymal stem cells[1].

The current use and the immense promise of stem cells from adipose tissue are due largely to three aspects that make the procedure simple:

1. The possibility of minimally invasive autologous transplants. Adipose-derived mesenchymal stem cells are obtained by lipoaspiration followed by centrifugation.
They can be directly injected into areas to be treated immediately after extraction, there in the operating theatre.

2. Cell expansion is not necessary. As said, the cells can be injected immediately after extraction, along with the lipoaspirate that surrounds them. They do not need to be pre-expanded in vitro. To complete the concept, the addition of the lipoaspirate means that what are injected are ‘‘stem cell niches’’ in which the cells are surrounded by a glycoproteic scaffold, including tissue factors that would be eliminated with digestion of the matrix if treated with collagenase—an indispensable step if expansion in vitro were necessary.

3. Age is no barrier. The procedure can be carried out at any time in a patient’s life since adipose stem cells are abundant even in the elderly and show the ability to repair lesionated tissues highly efficiently.
The efficacy of the technique has been confirmed repeatedly and under a variety of different conditions. How did this use of adipose-derived mesenchymal stem cells
originate and develop? And above all, what are the future therapeutic possibilities of this technique?