**2. Trophic factors correlated with ALS**

Previous studies have investigated the expression patterns of trophic factors in both in vitro cultures and animal models of ALS. Data accumulated in the last decade suggest that trophic factors are notable not only for monitoring ALS therapy and disease progression but also for potentially helping in ALS diagnosis. SCs, particularly MSCs, exhibit higher levels of NGF, BDNF, and VEGF expression after stimulation with protein extracts from the brains and spinal cords of transgenic SOD1 (G93A) rats (an animal ALS model) [21]. The fact of changing levels of these proteins at various disease stages demonstrates that they might be essential during ALS development and progression. Therefore, exploiting their potential in treatment is highly desirable. Unfortunately, their pharmacokinetic constraints, including their restricted ability to cross the blood-brain barrier (BBB) [22] and penetrate gray matter, limited bioavailability, and relatively short half-life [23], hinder their efficient use. Hence, other approaches of neurotrophin delivery, e.g., with viral vectors or by SCs grafts, are worth investigation. Recently, it has been reported that SCs derived from umbilical cord blood, an ethically sound source of SCs, express higher levels of neurotrophic factors when cultured under stress conditions [24]. Furthermore, in patients with ALS who received autologous transplant of bone marrow-derived stem/progenitor cells, slower disease progression was positively correlated with higher NTs expression levels [25].

The most promising studies aimed at assessing the involvement of neurotrophins and other growth factors in ALS and their potentials in ALS treatment are summarized below.
