Table 7 Cell-based therapies

Human subcutaneous fat extract

1. Vacuum-assisted liposuction of human adipose tissue from the abdomen, thighs, or upper arms

2. Cells are then removed from the aspirates through centrifuge

Cell-free, easy-to-prepare, lower risk of immunogenic rejection and genetic instability, and growth-factor–enriched liquid

Limited efficacy compared to cell-based therapies

Subcutaneous injection

Rat random pattern skin flap

Post-operative injections at 1.5-cm intervals of the skin flap caudally to cranially (a total of 5 injection points)

Cai et al. [29]

Adipose-derived stem cell (ADSC) therapy

1. Surgical removal of adipose tissue from the inguinal, finely minced and digested with lagenase

2. Two rounds of centrifugation to collect the layer with stromal cells, followed by flow cytometry cells sorting, induction of differentiation towards adipose cells by adipogenic substances

Abundant reserves with higher proliferating ability, easy harvest, and low donor site morbidity

Usually requires a long period of in-vitro expansion to produce a sufficient number of cells needed for transplantation

Intradermal injection

Rat random pattern skin flap

Single post-operative injection into the middle dermis along the long axis of the skin flap

Foroglou et al. [76]

Bone marrow-derived mononuclear cell

Isolation from bilateral femurs and tibias. Cells were then isolated using a strainer mesh, centrifugation, followed by a Ficoll-paque density gradient separation

Direct transplantation without in vitro cell expansion, enhances angiogenic growth factors bGFG and VEGF

Limited source

Subcutaneous injection

Rat random pattern skin flap

Injected at 10 points along the axis of the flap from the base to the distant end 2 days pre-operatively

Yang et al. [73]

Human amniotic membrane (h-AM)

AMs were obtained from placentas at the time of elective cesarean sections from overall healthy donors

Then, they were manually separated from the chorion, placed on the nitrocellulose membrane and cut into pieces small sheets

MAMs: The AM sheets are homogenized into microparticles with macro homogenization, freeze dried and filtered through a metal mesh o obtain microparticles

Cellular components with high tensile strength and tissue modeling power

Transplantation of the amniotic membrane sheet (AMS)

Smearing of micronized amniotic membrane (MAM)

Rat random pattern skin flap

AM sheet was transplanted into the flap site

MAM was smeared into the wound surface

Nazanin et al. [74]

Human umbilical cord matrix stem cells

Human umbilical cords were obtained from a local obstetrician from full-term Caesarian section births. Umbilical arteries and veins were removed. Whole-cell lysates were made from Wharton’s jelly cells by standard techniques using a lysis buffer

Robust proliferation and differentiation power for harvest in large quantity, High plasticity, and low immunogenicity

Subcutaneous injection

Mice axial epigastric skin flap pattern

Single post-operative injections at 10 evenly distributed points along the axis of the base of the flap to the distant end, each 1 cm apart

Leng et al. [28]

Mesenchymal stem cells

BM was flushed from the bones, isolated, and screened for MSC markers to separate BMMSCs. BMMSCs were then cultured, separated, and centrifuged

Most commonly used stem cell source due to its high efficacy to flap viability

Limited source and invasive harvesting procedures

Subcutaneous injection

Rat random pattern skin flap

Single post-operative injections of the BMMSCs at 12 points on each flap

Chehelcheraghi et al. [75]