Autologous Fat Grafting in the Treatment of Critical Limb Ischaemia
Autologous Fat Grafting in the Treatment of Critical Limb Ischaemia
Critical Limb Ischaemia (CLI) is a condition characterized by chronic ischemic at-rest pain,
 ulcers, or gangrene for more than 2 weeks in one or both legs, attributable to objectively
 proven arterial occlusive disease.CLI is associated with a high risk of lower amputation,
 diminished quality of life and mortality. Revascularization by either bypass surgery or
 endovascular recanalization is considered the first-choice treatment in patients with CLI.

 Revascularization is not always possible because patients with CLI often have severe
 comorbidities or because it is not technically feasible.

 On the basis of their well-recognized regenerative and angiogenetic properties, cell therapy
 with autologous bone marrow-derived mesenchymal stem cells (BMMSCs) has been proposed and
 tested in different animal models and in some human pathological conditions characterized by
 peripheral ischemia and wound formation.
The ADIPOCLI trial is an interventional monocentric trial in which the investigators will
 evaluate the safety, feasibility and potential efficacy of local administration of autologous
 adipose derived stromal/stem (ASCs) cell as treatment for pain and ulcers caused by CLI. If
 the results confirm safety, feasibility and show potential beneficial effects of the
 intervention regarding clinical parameters, a larger clinical research with longer follow up
 will be initiated focusing on efficacy. The objective of this clinical trial is to assess the
 efficacy and safety of ASCs inoculation in peri-tibial area, though reducing pain
 significantly in patients with CLI not eligible for revascularization.

 Autologous fat grafting is widely used for soft-tissue augmentation and replacement in
 reconstructive and aesthetic surgery providing a biocompatible, natural and inexpensive
 method. Noteworthy, recent reports have identified adipose tissue as the tissue in the body
 that contains the highest percentage of adult stem cells. These adipose derived stem cells
 (ADSCs) can undergo multilineage differentiation and may be crucial for the surgery purpose
 of healing ulcers as they have potent regenerative effects on endothelium and
 immunomodulatory properties.

 Adipose-derived stromal/stem cells (ASCs) are considered to be an attractive alternative to
 pluripotent cells with characteristics similar to BMMSCs. Compared with these latter cells,
 ASCs offer several advantages, including ease of isolation, less donor morbidity, relative
 abundance, and rapidity of expansion. Preliminary attempts with ASC cell therapy have been
 made to induce healing of ulcers developed in peripheral vascular diseases of some animal
 models and human disorders.

 The benefits of peritibial inoculation of autologous adipose tissue are the reduction of
 ischemic pain, the improvement of skin and muscle perfusion, the suspension of major
 amputation interventions and the healing of trophic lesions if present.

 The result of the intervention varies from individual to individual and depends on the
 engraftment of the transplanted material. In some cases the pain completely disappears. In
 others, the transplanted material may undergo varying degrees of reabsorption (from 50% to
 70%) and therefore a new transplant may be necessary after some time (6-12 months).

 The risks are linked to local complications of the procedure such as edema, ecchymosis, pain
 in the district of surgical aggression (the extent of these three manifestations varies from
 patient to patient, but are generally modest), dehiscence, bleeding of the wound, site
 infection surgical.

 The study has a total duration of 24 months. The recruitment phase lasts 18 months. After the
 surgical procedure, the patient will be followed for 6 months, during which he will undergo
 outpatient visits at 7 and 21 days; then at 1, 3, and 6 months. At each visit, the patient
 will be assessed for the amount of pain and the transcutaneous oximetry value. As in the
 usual clinical practice and in the diagnostic-therapeutic path of the arteriopathic patient,
 instrumental examinations (measurement of the ankle-brachial pressure index - ABI, arterial
 ultrasound Doppler lower limbs) are performed at the enrollment, at the twenty-first day and
 6 months after the procedure .

 The investigators will include 20 patients with CLI who satisfy the inclusion criteria.
 Inclusion and exclusion criteria were designed to select patients with CLI, not suitable for
 revascularization and who are in reasonable health condition to allow trial participation.
 Study participants are recruited from our own outpatient population or emergency room.
 Baseline characteristics are collected during the first visit and include medical
 examination, ABI and TcPO2 evaluation and Doppler ultrasonography to study the arterial axis
 of the limb. If CLI is diagnosed, the patient is hospitalized and undergoes an angiography
 study. Quality of Lyfe test is administered at hospitalization and at follow up.

 After angiogram, treatment of choice will be selected during the multidisciplinary vascular
 conference taking the individual condition of patients into account. Patients eligible for
 revascularization are submitted to open/endovascular surgery. Patient with CLI unsuitable for
 revascularization continue hospitalization being given best medical therapy, i.e. pain-killer
 drugs and prostanoids. Only to these class of patients an adjunctive treatment with local fat
 grafting is proposed. Information sheet is given to every patient after interview with
 investigators and informed consent is taken before the procedure.
Inclusion Criteria:

 -  Age > 18

 -  Established diagnosis of CLI according to TransAtlantic InterSociety Consensus (TASC
 II) guidelines

 -  Ankle oxygen partial pressure < 40 mmHg with no ischaemic lesions or < 60 mmHg with
 ischaemic lesions

 -  Tibial injections site free from ulcers

 -  Absence of comorbidities responsible for life expectancy < 6 months

 -  Non suitability for surgery (comorbidities or angiographic results)

 -  Informed consent taken

 Exclusion Criteria:

 -  Age < 18 years

 -  Inability of understanding and signing informed consent

 -  Tibial injections sites involved by ulcers

 -  Life expectancy < 6 months

 -  Unwillingness to attend follow up

 -  Any of the following: women who are or may be pregnant or women hoping to become
 pregnant; women who are breastfeeding; men whose partners hope to become pregnant
 during the treatment period