**1. Introduction**

Paralysis of the lower parts of the body (paraplegia) can be caused by any damage to the spinal cord [1, 2]. Traumatic and nontraumatic injuries are classifications of this disease [3]. Paraplegia causes severe and in most cases lasting changes in the patient's lifetime and lifestyle [4, 5].

Attempts to find a complete cure for paraplegia and several discoveries show that in adult mammalian, by the preparation of appropriate microenvironment, regeneration of spinal cord axons can be obtained [6]. But then, why can we see the huge delay in the processing of bench to bedside in spite of these findings? Unfortunately, spinal cord scientists find a new barrier in the regeneration field. In fact, axons do regenerate up and down through a graft or transplant placed at the damage site; however, when they reach healthy cord tissue beyond the injury zone, they fail to regenerate more at once [7]. The most important cause for this provision is that the axons of neural networks need to cross through during sufficient stabilized conditions which are unreceptive and intractable to new restoration. Successful elongated distance regeneration is probable only within destabilized neural tissues [8].

Recently, rapid progresses in multipotent stem cell (routinely called mesenchymal stromal/stem cells) investigations increase the interest of scientists to study about the cell therapy and regenerative medicine [9–11].

Mesenchymal stem cell transplantation in patients suffering paraplegia is considered as a strategy for increasing neuroregeneration [12–14]. Notably, because of the disproportion in the technique and method of MSC preparation for paraplegia treatment like how they administrate and which criteria are chosen for selecting patients, MSC transplantation is in the initial stages, and there is confusion about the consequences at present [15].

MSCs have various sources in the body including the bone marrow [16, 17], adipose [18], muscle [19], peripheral blood [20], umbilical cord [21–23], placenta [24], endometrial [25, 26] and menstrual blood [27–29], fetal tissue [30], and amniotic fluid [31]. Previous finding indicated that these clonal cells can adhere to plastic; express cluster of differentiation (CD) markers like CD73, CD90, and CD105 markers [32]; and can differentiate into adipogenic [33], chondrogenic [34], osteogenic [35, 36], and neurogenic [37–39] lineages in the experimental condition (in vitro). However, it can be observed many different reports in their strength and self-renewal potential [40]. Accordingly, when we compare previous surveys, variable or even conflicting results can be seen. The lack of uniform methods in MSC characterization, both in preclinical and clinical studies, contributes to this confusion. It is interesting that even the name "MSCs" has still been gradually questioned. Actually, an urgent demand is required to understand the novel sources and potencies of MSCs especially for applying in SCI treatment.

Previous findings showed that the optimistic effect of MSC in treatment of spinal cord and peripheral nerve injury ascribed to their differentiation ability. They can differentiate into various cell lineages and modulate the inflammation process and immunomodulatory responses. [41] MSCs can diminish cell apoptosis and secrete various neurotrophic factors [42, 43].

According to previous studies, transplanting enough cells is important to obtain the best outcome after MSC transplantation and also applying especial techniques for achieving the highest possible survival of MSCs. Likewise, it seems that repeated doses of MSC therapy might be helpful [44].

Findings obtained about clinical trials for SCI treatment demonstrated that the efficacy of MSCs in human studies is not beneficial like in preclinical studies [45]. For these reasons protocol standardization of basic and preclinical studies using MSCs should emphasize to translate to the clinical setting. This chapter book is based on preclinical studies and clinical trials dealing with MSC therapy for paraplegia with emphasis on the challenges in this field.
