Regulatory, ethical, and technical considerations on regenerative technologies and adipose-derived mesenchymal stem cells

Abstract

Since the early days of molecular biology, organ and tissue regeneration represents a challenging medical goal. However, only recently the advances in the understanding of the cellular components have enabled the promise to become a reality. In this vast panorama of new technologies, stem cells have progressively established themselves as the most effective and user-friendly regenerative therapeutic tool. Scientific meetings, workshops, conferences, and forums focused on translational science of regenerative technologies are today blooming all over the world. The audience questions and, even more, the very often controversial and conflicting explanations highlight the great deal of confusion regarding this new discipline that should be considered today a real independent medical specialty, requiring long-term studies and dedication. All the technologies able to separate and concentrate the adipose tissue (AT) and the stromal vascular fraction (SVF) and their related clinical applications need to comply with a complex but still unclear regulatory frame, becoming everyday more severe and restrictive, this limiting their practical use. The aim of this manuscript is to overview the current status of the regulatory frame and few related ethical considerations and to describe the evolution in the way the adipose-derived stromal vascular fraction (SVF) is isolated, extracted, and concentrated, as well as, of the ongoing researches and related future perspectives. Considerations on the most controversial and still unclear points related to the regenerative medicine and surgery, seen from the perspective of a research group who dedicated their entire professional life to this field, are also provided. Level of evidence: Not ratable.

Phenotypic Expression of Mesenchymal Stem Cells: Comparing Selective Tissueengineered Photostimulation Technique and Conventional Liposuction Technique.

“…Zocchi (2019) used an Adipose Tissue sonication, an ultrasonic-assisted lipoplasty, in order to emulsified the fat to isolate the stroma and ASCs maintaining the integrity and vitality of the tissue, and after flow cytofluorometry he found only 3,8% CD 105 positive cells . [28] Several authors have recommended not to use laser energy to obtain ASCs by stating that it diminishes cell viability significantly . In our experience, the use of STEP™ laser [18] 1210-nm with its Selective Tissue Engineering Photostimulation property does not affect viability of ASCs, and it is an optimal technique to obtain adipose tissue .…”

New perspectives in regenerative medicine and surgery: the bioactive composite therapies (BACTs)

“…In the majority of developed countries, only cells or nonstructural tissues-based therapies that do not cause relevant alteration of the biological characteristics of cells or tissues and preserving their original properties and functions, such as decantation, filtration, centrifugation, and mechanical disruption without relevant alteration are allowed in the clinical practice. These methods are included in the definition of minimal-grade manipulation (MGM), by which tissues are harvested, treated, and reimplanted during the same surgical session and inside the same operating room (Zocchi et al [16]).…”

“…Few are today, the exceptions where the use of cellular derivatives obtained through HGM and heterologous and allogeneic cells transplantation is allowed for daily practice [17]. Therefore, simple and well-consolidated laboratory procedures, such as enzymatic digestion of the adipose tissue with collagenase (0.075% dilution for 30 min at 37°), centrifugation, incubation, expansion in a Dulbecco's modified eagle medium (DMEM) with 10% fetal bovine serum and antibiotics and subsequent cultivation toward specific lines of cellularity, cannot be used as a routine choice for MSC transplantation and therapies [16].…”

“…The need to find more efficient strategies to support cell therapies made the authors focus on the basic principles of translational medicine. Thanks to a constant exchange of knowledge with major world leaders in this field and in parallel with the evolution from tissue engineering to advanced regenerative medicine, authors widened their approach integrating to the use of the bioactive composite grafts (BACGs) already described in previous articles [16] and the synergic action of the newest tools for improving grafted cell intake and survival. This novel 360° regenerative strategy is called bioactive composite therapies (BACTs) according to the precious suggestion of Prof. Fu-Chan Wei [18].…”

Regenerative assisted microsurgery (RAM) and regenerative assisted supermicrosurgery (RASM): the future of microsurgery?

“…Particularly enriched and tailor-made regenerative protocols called Bio Active Composite Grafts (BACG) have been recently developed to improve cell intake, differentiation, and proliferation inducing the host recipient site to act as real bioreactor, still remaining within the limits of the present legal frame for cells therapies [ 14 ].…”