Table 1.
Characteristics of the clinical studies on MM-AT products for the treatment of knee OA.
| Article | Study Type Blinding |
Type of Adipose Product (Device) |
Injected mL US Guidance |
Associated Treatment |
Control Group | Pts/Joints | Pts/Joints (Final F-Up) |
Age (Mean + SD) |
Sex (M/F) |
BMI (Mean + SD) |
OA Grade | Final F-Up (m) |
Main Results |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Aletto, 2022 [27] |
Prospective case series no |
Micro-filtered AT Lipocell (Tiss’You, RSM) |
10–15 mL no |
no | no | 123/123 | 123/123 | 57 | 57/66 | 27 | KL 1–3 | 6 | MM-AT is safe and ameliorates clinical and functional scores in early OA |
| Barfod, 2019 [28] | Prospective case series no |
MM-AT (Lipogems International Spa) |
10 mL no |
no | no | 20/20 | 20/20 | 49 ± 9 | n.r. | n.r. | n.r. | 12 | MM-AT is safe and improves functional scores |
| Baria, 2022 [29] |
RCT no |
MM-AT (Lipogems International Spa) |
7.9 ± 3.9 mL yes |
no | LR-PRP | 71/71 | 58/58 | 51.9 ± 2.4 (LR-PRP); 56.1 ± 1.7 (MM-AT) | 28/30 | 31.0 ± 0.8 (LR-PRP); 31.0 ± 0.9 (MM-AT) | KL 1–4 | 6 | MM-AT and LR-PRP show same clinical improvements |
| Boric, 2019 [30] |
Prospective case series no |
MM-AT (Lipogems International Spa) |
4–15 mL no |
no | no | 17/32 | 10/18 | 69 ± 12 | 7/3 | n.r. | KL 3–4 | 24 | MM-AT improves GAG content with relevant improvement |
| Cattaneo, 2018 [31] | Retrospective case series no |
MM-AT (Lipogems International Spa) |
10 mL no |
AS (n: 21) MEN (n: 14) |
no | 35/35 | 35/35 | 53 ± 12 (AS) 55 ± 11 (MEN) |
21/14 | 27 ± 4 | KL 1–3 | 12 | MM-AT is safe and adjuvates surgical treatment |
| Dallo, 2021 [32] |
RCT single blind (statistician) |
MM-AT (Lipogems International Spa) |
n.r. no |
no | LP-PRP+HA | 50/80 | 50/80 | 61.5 ± 9.5 (MM-AT); 62.5 ± 11.3 (LP-PRP+HA) | 23/27 | 26.3 ± 3.6 (LP-PRP+HA); 25.8 ± 5.1 (MM-AT) | KL 1–2 | 12 | LP-PRP+HA and MM-AT show same clinical improvement |
| Fan, 2023 [33] |
Prospective case series no |
MM-AT (Lipogems International Spa) |
6–8 mL yes |
no | no | 46/50 | 46/50 | 66.9 ± 1.0 | 28/18 | 32.0 ± 1.0 | KL 3–4 | 12 | MM-AT is safe and effective in moderate-to-severe OA |
| Ferracini, 2022 [34] | Prospective case series no |
MM-AT (Lipogems International Spa) |
3–50 mL yes |
Arthroscopy | no | 101/101 | 91/91 | 62.8 ± 10.1 | 44/47 | 25.3 ± 3.8 | KL 2–3 | 12 | MM-AT, associated with arthroscopy, reduces pain in early/mild OA |
| Giorgini, 2022 [35] | Retrospective case series no |
MM-AT (Lipogems International Spa) |
7 mL no |
Arthroscopy | no | 49/50 | 45/46 | 52.7 ± 10.0 | 24/25 | n.r. | KL 3–4 | 24 | MM-AT, associated with arthroscopy, is safe and effective |
| Gobbi, 2021 [36] |
Retrospective case series no |
MM-AT (Lipogems International Spa) |
5–21 mL yes | no | no | 75/120 | 75/120 | Mean 69.6 | 26/49 | Average 28.4 | KL 2–4 | 24 | MM-AT improves clinical, functional, and quality of life |
| Gobbi, 2023 [37] |
RCT single blind (clinical assessor) |
MM-AT (Lipogems International Spa) |
n.r. no |
no | LP-PRP+HA | 50/80 | 50/80 | 62.38 ± 11.88 | 39/41 | n.r. | KL 1–2 | 24 | MM-AT and LP-PRP+HA show same functional improvement, and safety, at mid-term f-up |
| Heidari, 2021 [38] | Retrospective case series no |
MM-AT (Lipogems International Spa) |
6–8 mL yes |
no | no | 220/334 | 25% pts lost to follow-up | n.r. | 125/95 | n.r. | KL 3–4 | 24 | MM-AT improves quality of life and can delay TKR |
| Heidari, 2020 [39] | Prospective case series no |
MM-AT (Lipogems International Spa) |
6–8 mL yes |
no | no | 110/110 | 110/110 | 42–94 | 60/50 | n.r. | KL 1–4 | 12 | MM-AT improves pain, function, and quality of life |
| Hudetz, 2019 [40] | Prospective case series no |
MM-AT (Lipogems International Spa) |
5 mL no |
no | no | 20/20 | 17/17 | n.r. | 15/5 | <30 (n: 13); 30–35 (n: 5); >35 (n: 2) |
KL 3–4 | 12 | MM-AT shows positive effect in late stages OA |
| Hudetz, 2017 [41] | Prospective case series no |
MM-AT (Lipogems International Spa) |
4–15 mL no |
no | no | 17/32 | 17/32 | 69 ± 12 | 12/5 | n.r. | KL 3–4 | 12 | MM-AT improves GAG content, pain, and clinical results |
| Kaszynski, 2022 [42] | RCT single blind (clinical assessor) |
MM-AT (Lipogems International Spa) |
n.r. no |
no | PRP | 54/54 | 40/40 | 57 ± 8 (PRP) 55 ± 8 (MM-AT) |
n.r. | 26 ± 3 (PRP) 27 ± 3 (MM-AT) |
KL 2–3 | 12 | MM-AT and PRP show same improvements in pain, symptoms, and functions |
| Malanga, 2021 [43] | Prospective case series no |
MM-AT (Lipogems International Spa) |
7.6 ± 2.3 mL yes |
no | no | 20/23 | 20/23 | 59.8 ± 6.5 | 11/9 | 28.6 ± 4.8 | Mild, Moderate, Severe |
12 | MM-AT is safe and effective |
| Magnanelli, 2020 [44] | Retrospective comparative no |
MM-AT (Lipogems International Spa) |
n.r. no |
HTO | HTO | 85/85 | 85/85 | n.r. | n.r. | n.r. | KL 1–3 | 12 | MM-AT, associated with HTO, improves the daily life activity |
| Mautner, 2019 [45] | Retrospective comparative no |
MM-AT (Lipogems International Spa) |
9 mL yes |
no | BMAC | 76/106 | 76/106 | 59 ± 1 (BMAC); 63 ± 11 (MM-AT) | 36/40 | n.r. | KL 1–4 | 21.6 ± 10.6 (BMAC); 13.1 ± 5.9 (MM-AT) | MM-AT and BMAC show same improvement in pain and function |
| Miles, 2022 [46] |
Retrospective case series no |
MM-AT (Lipogems International Spa) |
3.5–36 mL n.r. |
no | no | 39/56 | 37/53 | 71.1 | 19/20 | 28.4 | KL 1–4 | 22 | MM-AT improves pain, stiffness, and function |
| Panchal, 2018 [47] | Prospective case series no |
MM-AT (Lipogems International Spa) |
n.r. yes |
no | no | 17/26 | 17/26 | 68.27 ± 7.43 | 10/7 | 28.98 ± 4.50 | KL 3–4 | 12 | MM-AT is safe and effective in refractory severe OA |
| Peretti, 2018 [48] |
RCT (n.r.) |
MM-AT (Lipogems International Spa) |
19.1 ± 8.1 mL n.r. |
AD | AD | 39 (of 78 to be included, study ongoing) | 16 (8 cases vs. 8 control) | 56.25 ± 8.396 | 70%/30% | n.r. | KL 3–4 | 6 | MM-AT shows encouraging positive trend |
| Pintore, 2023 [49] | Prospective comparative no |
MM-AT (Tulip Soft Harvest GOLD System) |
10 mL no |
no | BMAC | 102/102 | 102/102 | 57.64 (BMAC); 61.94 (MM-AT) | 46/56 | 28.76 (BMAC); 26.76 (MM-AT) | KL mean 2.7 (BMAC); KL mean 2.5 (MM-AT) | 6 | BMAC and MM-AT show same improvement in pain and functions |
| Priano, 2022 [50] | Retrospective case series no |
Non enzymatic SVF (Hy-tissue SVF Separation System kit) |
8–10 mL no |
no | no | 25/25 | 25/25 | 53.2 ± 11.7 | 10/15 | 24.7 ± 2.1 | KL 2–3 | 6 | MM-AT relieves pain and improves stiffness and functions |
| Russo, 2017 [51] |
Retrospective case series no |
MM-AT (Lipogems International Spa) |
10–15 mL no |
ACLR, HTO, MEN (n: 24); arthroscopy (n: 6) | no | 30/30 | 30/30 | Median 43 | 31/9 | Median 26 | ICRS Grade 2–4 | 12 | MM-AT is safe and feasible in degenerative chondral lesions |
| Russo, 2018 [52] |
Retrospective case series no |
MM-AT (Lipogems International Spa) |
10–15 mL no |
ACLR, HTO, MEN (n: 24); arthroscopy (n: 6) | no | 30/30 | 22/22 | Median 43 | 31/9 | Median 26 | ICRS Grade 2–4 | 36 | MM-AT is safe in degenerative chondropathy in the mid-term |
| Santoprete, 2021 [53] | Retrospective case series no |
MM-AT (MyStemTM kit) |
n.r. no |
no | no | 84/102 | 84/102 | 57.3 ± 4.2 | 38/46 | n.r. | KL ≥ 2 | 12 | MM-AT improves pain, stiffness, and ROM |
| Screpis, 2022 [54] | Prospective case series no |
MM-AT (Lipogems International Spa) |
8 mL no |
no | no | 202/216 | 202/216 | 54.0 ± 9.0 | 97/105 | 26.8 ± 4.2 | KL 1–4 | 24 | MM-AT is safe and effective for symptoms |
| Ulivi, 2022 [55] |
RCT single blind (radiologist) |
MM-AT (Lipogems International Spa) |
6–8 mL no |
AD | AD | 78/78 | 66/66 | 60.7 ± 7.9 | 44/34 | n.r. | KL 3–4 | 13–42 | MM-AT, associated with AD, improves functions and MRI appearance |
| Van Genechten, 2021 [56] |
Prospective case series no |
MM-AT (Lipogems International Spa) |
8–10 mL yes |
no | no | 64 | 56/77 | 54.2 ± 9.1 | 31/33 | 27.2 ± 4.5 | KL 1–4 | 12 | MM-AT shows early clinical improvement but a mediocre response rate |
| Vasso, 2022 [57] |
Retrospective case series no |
MM-AT (Lipogems International Spa) |
10–15 mL no |
AD | no | 23/23 | 23/23 | 58 ± 8 | 8/15 | 28.0 ± 4.8 | ACR criteria 1–3 |
22.1 ± 4.2 | MM-AT, associated with AD, improves clinical and functional scores |
| Yu, 2023 [58] |
Prospective case series single blind (clinical assessor) |
MM-AT (Lipogems International Spa) |
6–8 mL no |
no | no | 20/40 | 20/40 | 54.63 ± 3.90 | 8/12 | 25.5 ± 2.86 | n.r. | 18 | MM-AT improves functions and pain, but not in the long term |
| Zaffagnini, 2022 [59] | RCT single blind (clinical assessor) |
MM-AT (Lipogems International Spa) |
5 mL no |
no | PRP | 108/108 | 108/108 | 54.5 ± 12.1 (MM-AT); 54.1 ± 10.6 (PRP) | 64/44 | 25.9 ± 4.3 (MM-AT) 28.0 ± 5.5 (PRP) | KL 1–4 | 24 | MM-AT and PRP show same improvements |
Abbreviations: ACLR = anterior cruciate ligament reconstruction; ACR = American College of Rheumatology; AD = arthroscopic debridement; AS = arthroscopic shaving; AT = adipose tissue; BMAC = bone marrow concentrate; BMI = body mass index; f-up = follow-up; M = male; F = female; GAG = glycosaminoglycans; HA = hyaluronic acid; HTO = high tibial osteotomy; KL = Kellgren–Lawrence; LR-PRP = leucocyte-rich–platelet-rich plasma; m = months; MM-AT = minimally manipulated adipose tissue; MEN = meniscectomy; MRI = magnetic resonance imaging; OA = osteoarthritis; Pts = patients; RCT = randomized clinical trial; ROM = range of motion; SD = standard deviation; TKR = total knee replacement; US = ultrasound; n.r. = not reported.