There has been increasing attention toward stem cell therapy in different fields, including dermatology, in recent years. Mesenchymal stem cells have been applied to various dermatologic conditions, especially in wound healing, scars, and rejuvenation [20]. Considering striae distensae as a kind of atrophic scar, there haven’t been any clinical trials conducted to evaluate the effectiveness of this trend regarding striae treatment.

This randomized clinical trial evaluated the efficacy of human umbilical cord mesenchymal stem cells plus microneedling compared to microneedling alone in striae distensae. Three 3-weekly sessions of dermal injection of conditioned media following microneedling resulted in notable patient and physician satisfaction compared to microneedling and normal saline.

Microneedling has been shown to be an effective treatment modality for striae distensae by increasing the production of elastin and collagen and enhancing epidermal thickness [11, 32, 33]. Several studies have demonstrated that microneedling is as effective as CO2 fractional laser in improving stretch marks, with less downtime, greater availability, and more cost-efficiency [30, 34, 35]. According to this study, microneedling plus normal saline did not lead to achieving satisfaction for either patients or physicians. Despite observing a trend in biometric parameters, only changes in dermal and complete thickness, as well as skin density, were defined as significant.

In 2023, Abbas et al. demonstrated that four monthly sessions of both microneedling and microneedling combined with Ascorbic Acid on 28 patients were safe and effective in treating striae distensae three months after completing the protocol [36]. Another study in 2019, conducted on 20 women with striae distensae, compared the effectiveness of non-ablative fractional laser (NAFL) to microneedling in five monthly sessions. Both modalities were effective based on clinical and histologic evaluation (p < 0.01), while laser had more downtime [34].

Our study revealed conflicting clinical findings, as both patient and physician assessments were unsatisfactory in control group. It seems that this contradiction might be due to the lower number of sessions, and further follow-ups were required, although some improvements were observed in biometric evaluation. Similar to resurfacing lasers, microneedling promotes collagen synthesis and dermal remodeling through dermal injury [29, 34, 37]. Concurrently, current study showed a notable increase in dermal and complete thickness and skin density using microneedling, which might be attributed to an increase in collagen bundles.

According to several systematic reviews, combination therapy is the most approved approach to treating striae distensae (SD) [8, 13]. The combination of microneedling with platelet-rich plasma (PRP) has been identified as a satisfactory approach to SD treatment [38]. PRP is considered a form of regenerative medicine containing numerous growth factors. According to Abdel-Motaleb et al.’s study in 2022, three monthly sessions of microneedling plus PRP on stretch marks in 40 patients resulted in notably higher patient and physician satisfaction and a marked increase in collagen and elastin fibers compared to microneedling alone [38]. Similarly, in our study, the patient and physician assessments were significantly higher in the MSCs plus MN group. Additionally, there was a significant enhancement in epidermal, dermal, and complete thickness, as well as density, in this group.

While combination therapy is generally considered the best approach to SD, contradictory results have been observed in different studies involving various modalities [39,40,41]. A review study conducted in 2021 to evaluate the effectiveness of the PRP method in treating striae distensae revealed that the published studies in this field did not provide strong evidence of the effectiveness of PRP [42].

Since the emergence of MSCs, many studies have applied the regenerative effects of these cells in a wide range of medical fields from cardiology to neurology. Several studies have implicated MSCs as a promising approach to treating scars, wounds, and skin regeneration in recent years [43, 44]. In this study, three monthly sessions of a combination of human Wharton’s jelly mesenchymal stem cells (hWJMSCs) with microneedling indicated statistically more patient and physician satisfaction with a significant increase in all skin ultrasound parameters (epidermal, dermal, and complete thickness and density). However, the cutometer parameters didn’t show any significant change. In 2023, Joo et al. [45] utilized three monthly sessions of non-ablative laser plus human stem cell-conditioned medium (HSCM) and compared it to laser alone on hypertrophic scars. The thickness changes of scars were significant in the combined group comparing to the control (p = 0.01). In 2021, Park et al. [46] compared the drug delivery of human stem cell-conditioned media (HSCM) following fractional CO2 laser to laser alone in the treatment of atrophic acne scars. Two months after a single session, scar volume was reduced by 23.5% in the combination approach compared to 15% in the control, which wasn’t statistically significant (p = 0.143). However, the volume of the skin pores was significantly reduced by 37.6% (T) versus 15.9% (C) (p = 0.006). In a similar study conducted in the same year [47], the efficacy of topical stem cell-conditioned medium (SC-CM), PRP, and NS following three monthly sessions of fractional CO2 laser resurfacing for atrophic acne scars was assessed. Despite a significant increase in dermal collagen in the SC-CM and PRP groups compared to the control, better clinical improvement was observed in PRP compared to SC-CM (p = 0.63). Similar to recently developed studies, some contrasting findings were observed regarding clinical and biometric comparison in the combination of MSCs with MN to MN plus NS in this trial. This indicates the need for further studies to clinically evaluate the effectiveness of stem cells in atrophic scars and striae distensae with more intervention sessions and longer follow-up. It could be suggested that due to the different pathological characteristics of atrophic scars from hypertrophic scars [48], more intervention sessions might be required to achieve statistically promoted outcomes, particularly in viscoelasticity and pure elasticity, since this promotion is somehow observed in our study and these studies. According to in vitro and animal studies, mesenchymal stem cells (MSCs) have an anti-fibrosis effect, the potential to reshape the microvascular structure, form complex hybrid systems, induce collagen synthesis, and remodel ECM, all of which are considered to play a role in the pathophysiology of SD [19, 49, 50]. Wharton’s jelly mesenchymal stem cells are considered a particularly better option due to their role in embryonic growth and development as well as tissue repair, compared to other cells [23]. Stromal vascular fraction (SVF), another regenerative modality, was employed in 2023 to evaluate its effectiveness in the treatment of burn scars [51]. Similar to our findings, three months of sessions involving a combination of SVF and fractional CO2 laser led to higher patient and physician satisfaction compared to laser alone. Additionally, epidermal thickness, complete density, and skin density sonography revealed a significant change in the combination group.

Combination of MSCs with MN (microneedling) has also been practiced in several studies, especially for rejuvenation with promising outcomes. In a randomized split-face study, five bi-weekly sessions of hUC-MSCs-CM (human umbilical cord mesenchymal stem cell-conditioned media) plus MN were employed on thirty subjects suffering from skin aging [52]. Compared to MN alone, the Combination group exhibited more assessor and patient satisfaction, as well as significant improvements in skin brightness parameters (reduced melanin index, ultraviolet spots, and brown spots) and skin texture (reduced wrinkles and pores, and increased skin elasticity) (p < 0.05) two weeks after the final session. Meanwhile, there were no obvious differences observed in skin hydration, trans-epidermal water loss, and the erythema index. In a separate split-face study in 2023, Adipose tissue stem cell-derived exosomes (ASCEs) with microneedling were applied in three sessions with 3-week intervals for skin rejuvenation and compared to MN alone [53]. Following 6 weeks from the last treatment, the clinical evaluation was much more remarkable in the combination group (p = 0.023). Significant improvement was observed in skin elasticity (p = 0.002), skin hydration (p = 0.37), skin pigmentation (p = 0.044), and greater density of collagen and elastic fibers in the combination group. Another study showed that five bi-weekly sessions of skin needling and topical application of amniotic fluid mesenchymal stem cell-derived conditioned media (AF-MSC-CM) would significantly result in improving skin (p < 0.001) and better remodeling of the dermal structures [54].

Up to date, we haven’t discovered any clinical trials evaluating the effectiveness of human mesenchymal stem cells in stretch marks and comparing it in combination with microneedling (MN), one of the common traditional methods, to MN alone. Our study represented the first clinical trial evaluating the effectiveness of mesenchymal stem cells for the treatment of striae.

Supporting previous clinical trials in scars, our findings suggest that MSCs might be a promising option. The limitations of the current study include a low number of sessions, a short follow-up, and a small sample size, which may result in non-significant biometric differences between the two groups.