Review Article

Stromal Vascular Fraction and Amniotic Epithelial Cells: Preclinical and Clinical Relevance in Musculoskeletal Regenerative Medicine

Table 2

In vitro, in vivo, and clinical studies on SVF in cartilage regeneration.

Experimental modelTreatment groupsEvaluationsResultsRef.

In vitro:
Human chondrocytes () from healthy donors
hSVF or hADSCs () from abdomen
In vivo:
10 BALB/C nude mice (6 wks) with subcutaneous pouches
Allogenic SVF or ADSCs
Allogenic chondrocytes ()
In vitro:
Group 1: SVF pellet
Group 2: ADSC pellet
Group 3: chondrocyte pellet
Group 4: SVF+chondrocyte pellet (4 : 1)
Group 5: ADSCs+chondrocyte pellet (4 : 1)
In vivo:
Group 1: no treatment
Group 2: SVF+chondrocytes (4 : 1) in 2% alginate
Group 3: ADSCs+chondrocytes (4 : 1) in 2% alginate
Group 4: chondrocytes
In vitro:
Histology
GAG quantification
Cell proliferation
In vivo:
Histology
GAG quantification
IHC (COLL II)
In vitro:
1 mo
Group 4: ↑ GAG, chondrocytes % than group 5
In vivo:
2 mo
Group 2: ↑ GAG, COLL II protein than groups 1, 3, and 4
[43]

In vivo:
8 skeletally mature Dutch milk goats () with 2 osteochondral defects in the right troclea femoris and 2 defects in the right medial femoral condyles
Autologous SVF or ADSCs ()
COLL I/COLL III scaffold ()
Group 1: scaffold
Group 2: scaffold+SVF
Group 3: scaffold+ADSCs
Gross evaluations
Histology
Micro-CT
1 mo
Group 1: =gross appearance score, histological score than groups 2 and 3.
4 mo
Group 2: ↑ cartilage and SB regeneration than groups 1 and 3
Group 2: ↑ hyaline cartilage; ↓ fibrocartilage, cartilaginous tissue in SB than group 3
[44]

In vivo:
30 small tail Han sheep (6 mo) with OA in the right knee
Autologous SVF () or ADSCs from cervicothoracic region
HA scaffold (600–1500 kDa) (2.5 ml)
Group 1: saline (5 ml)
Group 2: scaffold
Group 3: scaffold+ADSCs ()
Group 4: scaffold+ADSCs ()
Group 5: scaffold+SVF
IHC (COLL X, SDF1)3 mo
Group 5: ↓ COLL X protein than groups 3 and 4.
Group 5: ↑ SDF1 protein than groups 1 and 2
[7]

In vivo:
9 NOD/SCID mice with injured cartilage
hSVF () from abdomen
Group 1: PBS
Group 2: SVF+PRP
Movement recording
Histology
Histomorphometry
45 days
Group 2: ↓ time required that mice could move, cartilage lesion area; ↑ formed neocartilage than group 1
[45]

Clinical trial:
13 pz (65-82 yrs) with bilateral severe OA
Allogenic SVF () from abdomen
Group 1: SVFClinical evaluation1 and 6 mo
Group 1: ↓ JKOM score, WOMAC score, VAS score than presurgery.
No differences between 1 and 6 mo
[46]

Clinical trial:
18 pz () with OA
Autologous SVF (35 ml) from abdomen
Group 1: SVFClinical evaluation
Radiography
3, 6, and 18 mo
Group 1: ↓ VAS score, WOMAC % than presurgery. No infection, thromboembolism, adverse reaction
18 mo
Group 1: =outerbridge score than presurgery
[47]

Clinical trial:
10 pz (≥50 yrs) with idiopathic knee OA
Allogenic SVF (5 ml) from abdomen
Group 1: SVF+PRP (3 ml)Clinical evaluation
SF analysis
3, 6, 12, 18, and 24 mo
Group 1: ↓ WOMAC total, WOMAC stiffness, WOMAC pain, WOMAC physical function; ↑ six-minute walk distance than presurgery
24 mo
Group 1: no atypical cells in SF, restore SF properties, synovial metabolism; ↓ cartilage pathology than presurgery
[48]

Clinical trial:
4 pz (23-74 yrs) with OA of both knees
Autologous SVF (, , , and ) from periumbilical region
Group 1: SVF+PRP (3 ml) (4 injections every month)Clinical evaluation12 mo
Group 1: ↑ KOOS score pain, symptoms, ADL, sport/rec function, knee-related QOL. Pz regained normal functional activity
[49]

Clinical trial:
30 pz (>18 yrs) with OA
Autologous SVF from abdomen
Group 1: arthroscopic microfracture
Group 2: arthrosopic microfracture+SVF+PRP (5 ml)
Clinical evaluation
BM edema
12 mo
Group 2: ↓ BM edema than group 1
Group 1: ↓ WOMAC score during time
18 mo
Group 2: ↓ WOMAC score during time
Group 2: ↓ WOMAC score; ↑ Lysholm score than group 1
[50]

Clinical trial:
33 pz (>38 yrs) with OA
Autologous SVF (6 ml with cells) from abdomen
Group 1: arthroscopic microfracture
Group 2: arthroscopic microfracture+SVF
Clinical evaluation
BM edema
12 mo
Groups 1 and 2: ↓ VAS score, WOMAC score during time
24 mo
Group 2: ↓ VAS score, WOMAC score, Outerbridge score than group 1
Groups 1 and 2: ↑ Lysholm score during time
Group 2: ↓ BM edema during time
Group 1: ↑ BM edema during time
[51]

Clinical trial:
16 pz () with bilateral OA of grade II or III
Hyaluronic acid (4 ml)
Autologous SVF (4 ml) from abdomen
Group 1: arthroscopic debridement+SVF
Group 2: arthroscopic debridement+HA
Clinical evaluation
Radiography
1, 3, 6, and 12 mo
Group 1: ↓ VAS, WOMAC pain, WOMAC stiffness; ↑ ROM during time
Group 2: ↑ VAS, WOMAC pain, WOMAC stiffness; ↓ ROM than group 1
1 mo
Group 2: ↑ ROM during time
3, 6, and 12 mo
Group 2: ↓ ROM during time
1 and 3 mo
Group 2: ↓ VAS during time
6 and 12 mo
Group 2: ↑ VAS during time
Group 1: ↑ MOCART score during time
Group 1: ↑ MOCART score, complete tissue filling than group 2
Group 2: ↓ MOCART score during time
[52]

Clinical trial:
26 pz () with full-thickness chondral defect of the talar dome
Autologous SVF ( MSCs) from buttock
Group 1: arthroscopic marrow stimulation
Group 2: arthroscopic marrow stimulation+SVF
Clinical evaluation
Radiography
16-25 mo
Groups 1 and 2: ↓ VAS score; ↑ AOFAS score during time
Group 2: ↓ VAS score; ↑ AOFAS score, Tegner score, MOCART score than group 2
[53]

Clinical trial:
1 pz (36 yrs) with traumatic osteochondral lesion of the right medial femoral condyle 8 mo after injury
Autologous SVF () from abdomen
Group 1: microfracture+SVFClinical evaluation
BM edema
Radiography
24 mo
Group 1: ↑ IKDC, EQ-VAS than presurgery
12 and 24 mo
Group 1: recovery of CT; ↓ BM edema than presurgery
[54]