**7. Conclusions**

scalp tissue with promising results [127]. Recently, human DP cells from scalp tissue have been embedded into dermal–epidermal composites (DECs) and formation of complete HF

By ongoing studies, it was realized that not only the close environment of HF but also the macro environment of HF is important in the growth induction of HF. As the adipocyte stem cells (ASCs) secrete growth factors and stimulate hair growth pathways and the activation of hair follicle stem cell by adipocyte lineage cells has been shown, ASCs and ASC‐conditioned medium (ASC‐CM) have been investigated in hair regeneration studies. DPCs which are cultured in ASC‐CM showed increased proliferation. These studies suggested a role for ASCs in

Bone marrow mesenchymal stem cells (BM‐MSCs) have also been used to induce hair induc-

In a randomized placebo‐controlled trial, topical application of a commercially available solution containing HFSCs in male patients with AGA was found to be effective in the induction of hair growth and reduction of hair loss [130]. Supernatant of BM‐MSC culture overexpressing Wnt1a has been shown to increase hair producing ability of DP cells. Additionally, intradermal injection of concentrated solution of the above mentioned supernatant enhanced the transition from telogen to anagen in mouse. Also, negative effect of a 5‐DHT on hair related genes was restored with the addition of Wnt‐CM. Study indicated a role for Wnt1a from

The effect of intradermal injection of commercially available ASC‐CM product (containing hepatocyte growth factor, fibroblast growth factor‐1, granulocyte colony‐stimulating factor, granulocyte macrophage‐colony‐stimulating factor, interleukin‐6, vascular endothelial growth factor, and transforming growth factor β‐3) to 22 AGA patients (11 males, 11 females) has been studied. Patients were treated in six sessions at 3–5‐ week interval. Six male patients were also on finasteride treatment. Half‐side comparison study has been undertaken in 10 patients. Hair counts were increased in all patients according to trichogram assays. In comparison study, hair count was increased in both side of the scalp, however, the increase was higher in the treatment side compared to the placebo side. The response in the placebo side is suggested to be related to the effect of injection itself or the diffusion of the solution to the

In another study with the same product, 27 patients with FPHL were treated with the solution (ASC‐CM) weekly with concurrent use of microneedling roller. Retrospective assessment of the results revealed significant increment in the hair density and thickness after 12 sessions

An evidence to the alternative mechanisms of stem‐cell therapy is the "stem cell educator therapy" which has been used for its immune modulation effect in nine AA patients. Cord blood stem cells (CB‐SCs) have been used to be introduced to patient's blood in a closed loop

tion *in vitro* assays and tested for HF formation capacity in mouse models [116].

has been observed [128].

334 Hair and Scalp Disorders

alopecia treatment [117, 129].

other side [131].

[129].

**6.4. Studies on the stem‐cell therapy in alopecia**

MSCs in hair regeneration therapies for alopecia [116].

Although the scientific data to support the validity of mesotherapy as a treatment option in alopecia is still lacking, there is an increasing interest in its use. Hair mesotherapy is not yet approved in the treatment of alopecia and the existing studies give variable results. Therefore, long‐term studies on a large cohort of patients are necessary to document its efficacy and safety in alopecia treatment and to standardize the treatment protocols. Hair mesotherapy can be used as an alternative intervention in the treatment of AA, AGA, and telogen effluvium in patients without systemic diseases.

Despite the increasing interest in microneedling in the treatment of different types of alopecia, further randomized controlled trials are required to assess the efficacy of microneedling on alopecia.

Literature suggests PRP as an effective tool in AGA patients. PRP can be considered as an alternative treatment in AA patients not responsive to corticosteroid treatment or in the patients developing side effects due to steroid injections.

LLLT seems to be a safe and effective treatment option for patients with AGA, but more long‐term placebo‐controlled studies are needed to define the beneficial effects of laser/light sources for the management of this disease. The effects of laser/light sources are shown in many studies as mentioned above in AA. However, larger placebo‐controlled studies should be performed to evaluate the beneficial and adverse effects of these devices.

There is no conclusive data regarding the efficacy, applicability, and method of stem‐cell therapy in the treatment of alopecia, however, it still remains as a potential intervention. Further studies are required with improved techniques to overcome challenges in regenerating intact HFs before clinical use. Also the cost and availability of such bioengineering therapies must be taken into consideration. Similar to the current follicular unit transplantation (FUT) therapy, in future, it is expected to transplant a complete HF created by stem cell technology and be able to treat various types of alopecia.
