TABLE 10.
Studies regarding mesenchymal stromal cell-conditioned medium for skin rejuvenation in humans.
| MSC source | Method of tissue extraction | Type of study | Indication and population | Groups of treatments and via of administration | Follow-up (days) | Assessment | Main outcome | Other outcomes | |
| El-Domyati et al., 2020 | Human amniotic fluid | − | Prospective observational study | Volunteers with facial aging 49.9 ± 5.59 years 3:7 (M:F) | 1 ml of MSC-CM was topically applied to the treated group - Skin needling (control) - Skin needling+MSC-CM (n = 10) |
30 | Clinical examination, photographs, histology (HE, MT, Orcein stains) | The percentage of improvement was higher in the MSC-CM group compared with controls (65.40 ± 11.34 vs. 38.60 ± 9.02; p < 0.001) | Remodeling of the dermal structures was observed mainly on the combined side. Epidermal thickness increased on both treated sides |
| Kim J. et al., 2020 | Human umbilical cord | Umbilical cord dissection | Randomized, investigator−blinded, prospective, split−face comparison study | Patient with large pores or wrinkles on the face that underwent laser resurfacing (42.2 years, range 25–56) | Topical application twice a day - MSC−CM cream (control) - MSC−CM cream and serum (n = 23) |
21 | Macroscopic appearance (photography, area of microcrusts), skin biophysical parameters (TEWL, SCH, erythema) | The percentage of the total microcrust area was significantly smaller in the MSC−CM cream and serum group than in the cream group (2.70 ± 0.56 vs. 3.13 ± 0.76, p < 0.05) | A slight increase in SCH values were observed in both groups without changes in TEWL. Patient satisfaction was similar in both groups. No adverse events were reported related to MSC-CM application |
| Abdel-Maguid et al., 2019 | Human amniotic fluid | − | Prospective randomized split-face study | Patients with atrophic acne scars | - Group I (n = 17). FxCR+topical MSC-CM on one side of the face or FxCR plus saline on the other side - Group II (n = 16). FxCR+ topical PRP on one side of the face or FxCR+ topical MSCs on the other side |
90 | Macroscopic appearance (photography), histology (HE, MT), qRT-PCR | In both groups, scars improved after treatment. No significant difference in clinical improvement of acne scars was observed between the FxCR+MSC-CM and FxCR, while better and faster improvement was detected on FxCR+PRP side compared with FxCR +MSC-CM side | All patients developed transient erythema and mild edema without differences between groups. Dermal collagen was increased and procollagen type I gene was upregulated in both FCL/PRP and FCL/SC-CM sides compared with FCL only sides |
| El-Domyati et al., 2019 | Human amniotic fluid | − | Prospective observational study | Patients with atrophic acne scars. | Topical application after five sessions of microneedling with dermaroller - 1 ml of MSCs−CM - Non-treated (n = 10) |
90 | Clinical examination, histology, histometric analysis | There was a significant increase in the improvement percentage of acne scars on the MSC−CM-treated side (65.40 ± 11.34 vs. 38.60 ± 9.02) | Improvement of character of collagen and elastic fibers was noticed, especially on MSC−CM side. Significant increase in epidermal thickness on both sides of face was detected. Erythema and slight edema appeared on both cheek sides |
| Park C. S. et al., 2019 | Human adipose tissue | − | Prospective randomized split-face study | Patients with atrophic acne scars | Topical application twice a day after laser treatment - 80% MSC-CM+20% HA - HA (n = 15) |
60 | Scar volume and erythema were objectively evaluated using an Antera 3DVR CS | Scar volume was reduced by 23.5% in MSC-CM side vs. 15.0% in control side, and the volume of the skin pores was reduced by 37.6% in MSC-CM side vs. 15.9% in control side | The erythema increase was lower in MSC-CM side (2.8% vs. vs. 3.1%) |
| Prakoeswa et al., 2019 | Human amniotic membrane | − | Randomized, matching pair, clinical trial | Healthy women with clinical photoageing (50.31 ± 5.1 years) | 3 ml topically applied every 2 weeks after microneedling - Normal saline (control) - MSC-CM (n = 48) |
56 | Macroscopic appearance (photography, Glogau scale) | MSC-CM group showed better improvements in pore and wrinkle | Skin tone did not improve in either of the groups |
| Kim et al., 2018 | Human umbilical cord | − | Prospective observational study | Healthy women with face wrinkles (range 18–55 years) | 10% MSC-CMs in cream base topically applied daily on face skin (n = 22) | 28 | Macroscopic appearance (photography), ultrasound | Dermal density was increased by 2.46% compared before treatment | Wrinkles of eye-end area were decreased after the treatment. No irritation, stinging, or any adverse reactions were observed |
| Xu et al., 2016 | Human adipose tissue and placenta | − | Prospective randomized clinical trial | Healthy volunteer | Intradermal injections - AT-MSC-CM+HA - P-MSC-CM+HA - HA (control) (n = 6/group) |
15 | Biophysical measurements | Erythema, melanin, elasticity, TEWL, and hydration showed improvement in hAD-MSC-CM and hP-MSC-CM compared with the control group | Only the melanin index of the hAD-MSC-CM group was significantly lower than that of the hP-MSC-CM group |
| Zhou et al., 2016 | Human subcutaneous adipose tissue | Liposuction | Prospective observational study | Patients with facial wrinkles and patients with atrophic acne scars. 36.4 years (range 24–50) 5:6 male:female | 3 ml topical application after FxCR - MSC-CM - DMEM (n = 9 with facial wrinkles n = 13 with atrophic acne scars) |
90 | Macroscopic appearance (photography), subjective satisfaction scale, biophysical measurements (erythema, melanin, TEWL, elasticity, skin surface roughness, hydration), and histology (HE, MT, Gomori’s aldehyde fuchsine staining) | Subjective satisfaction (2.35 ± 0.69 vs. 2.08 ± 0.76, p < 0.05) and objective clinical assessment (2.78 ± 0.45 vs. 1.89 ± 0.60, p < 0.05) were higher in MSC-CM group than DMEM | Elasticity and hydration were significantly higher in MSC-CM side, while TEWL and roughness were lower. Increased dermal collagen and elastin density were found in MSC-CM side. No adverse events were reported in the study |
| Lee H. J. et al., 2014 | Human embryo | Prospective randomized controlled observer-blind split face study | Healthy individuals with face wrinkles (51.6 years, range 41–64) | Treatment every 2 weeks - Microneedling (control) - Microneedling + 1.5 ml of MSC-CM (n = 25) |
84 | Macroscopic appearance (photography), biophysical parameters (erythema, melanin, elasticity) | Overall satisfaction was higher in MSC-CM group than in controls (3.25 ± 1.26 vs. 2.72 ± 1.45) and also objective clinical improvement (1.92 ± 0.42 vs. 1.49 ± 0.48) | Erythema, melanin, and elasticity improved more in MSC-CM group. No serious adverse events were observed; only mild pain, erythema, and desquamation were found | |
| Seo et al., 2013 | Human embryo | − | Prospective randomized controlled, investigator-blinded, split-face study | Healthy volunteers. 53.8 ± 3.21 years, range 41–64 | - Microneedling fractional radiofrequency (control) - Microneedling fractional radiofrequency+MSC-CM (n = 15) |
28 | Macroscopic appearance (photography), biophysical parameters (SCH, erythema, melanin, wrinkles, elasticity), histology (HE), IHC | More improvements of wrinkles and overall skin appearance were observed in combined treatment compared with microneedling alone (2.06 ± 0.70 for radiofrequency and 2.20 ± 0.68 for the combined treatment, p < 0.05) | Patients’ overall satisfaction scores were higher in combined treatment (2.35 ± 0.42 vs. 2.00 ± 0.65). SCH showed a greater increase in the combined treatment. Similar decreases in erythema and melanin index were observed in both groups. No serious adverse events were reported |
| Zhou et al., 2013 | Human subcutaneous adipose tissue samples | Liposuction | Prospective observational study | Healthy volunteers. 24–33 years 5:14 male:female | Topical application after laser treatment: - FxCR 8 mJ, with MSC-CM - FxCR 8 mJ with DMEM - FxCR 16 mJ with MSC-CM - FxCR 8 mJ with DMEM (n = 19) |
21 | Macroscopic appearance (photography), biophysical parameters (TEWL, erythema, melanin, elasticity), histology (HE, MT, Gomori’s aldehyde fuchsine staining), qT-PCR | The MSC-CM-treated side shows less erythema and less pigmentation | MSC-CM side also showed a greater reduction of TEWL. There were no differences in elasticity parameters. The mRNA of type III procollagen in MSC-CM-treated group was 2.6 times that of control. No adverse events were reported |
AT, adipose tissue-derived; CM, conditioned medium; DMEM, Dulbecco’s modified Eagle medium; FxCR, fractional carbon dioxide laser resurfacing; HA, hyaluronic acid; HE, hematoxylin and eosin; hCB, human cord blood; hESC, human embryonic stem cell; IHC, immunohistochemistry; MSCs, mesenchymal stromal cells; MT, Masson’s trichrome; P-MSCs, placenta-derived mesenchymal stromal cells; qRT-PCR, real-time quantitative polymerase chain reaction; PRP, platelet-rich plasma.