Joris van Dongen

333 General discussion and future perspectives re-educates damaged tissue by tSVF of adipose tissue. Although, no significant improvements have been described as a result of tSVF or lipofilling applied to ‘ordinary’ ageing skin, significant improvement of skin quality have been described in cases where skin changes occurred due to a disbalance of extracellular factors as in dermal scarring and wound healing. 31-34 Yet, formal proof derived from randomized prospective trials is lacking thus far. In this thesis, a prospective randomized placebo-controlled double blinded clinical trial was performed to accelerate postoperative wound healing by tSVF in order to reduce postoperative scarring. tSVF was injected in the wound after a breast reduction, while the contralateral breast received a placebo injection with 0.9% NaCl. After six months, a significant improvement in scar appearance measured with the validated patient and observer scar assessment scale (POSAS) was shown by both patient as well as observer. However, twelve months postoperative scar appearance was comparable between the tSVF and control group. Many of the included patients noticed a faster healing of the wound in the first weeks postoperative. This indicates that tSVFmight play a more significant role in accelerating wound healing than as anti- scarring treatment. Unfortunately, this trial used an one-time injection, while a second administration might have had a more profound long-term influence. To date, many studies have investigated if lipofilling or any regenerative component i.e. ASCs or SVF can accelerate wound healing. Yet, all of these studies lack a proper designed studywith validated outcome measurements to reliably conclude that (or substrate of ) lipofilling accelerate dermal wound healing. Since evidence of the skin rejuvenating effect of lipofilling on ‘ordinary’ aged skin seems to be lacking, lipofilling for skin rejuvenation purposes solely should ideally only be offered in prospective randomized and placebo-controlled trials. Controlled randomized clinical trials are study types that can only show, with the highest predictability, whether a treatment, that seemed to be beneficial as apparent in initial case reports or retrospective studies, indeed is evidence-based working and effective. In general, both patients as well as clinicians expect an elective non-life saving and often self-paid treatment delivers an effective, efficient, satisfactory end result that was originally aimed for. Without well-defined readouts, such as third person analyses on blinded samples, claims in case reports and retrospective studies suggesting that lipofilling is effective for the use of skin rejuvenation are actually non-evidence based and thus not true nor valid. These claims, however, contribute to the hype that ASCs in lipografts are responsible for the questionable rejuvenating effect on skin. Moreover, the terminology of ASCs in communication between clinicians and patients contribute to this aforementioned hype as well. Till recently, adipose derived stromal cells (ASCs) were named adipose derived stem cells. However, ASCs are not stem cells for several reasons. First, stem cells are capable of self-renewal and have an unlimited proliferation