**5. Conclusions**

parameters such as the increase in the left ventricular ejection fraction (LVEF) and decreases in end-diastolic volumes and LV end-systolic volumes were observed up to 18 months after treatment [102]. RIMECARD is a phase I/II clinical trial that has demonstrated the safety and efficacy of the intravenous infusion of UC-MSC in patients with chronic heart failure and reduced ejection fraction. Improvements in left ventricular function, functional status, and the

Cell therapy has been introduced as a new therapeutic attempt to restore blood flow and attenuate ischemia promoting collateral vessel formation in CLI. In January 2017, a Phase III

the U.S. Food and Drug Administration (FDA). Data from previous studies have shown that by increasing tissue perfusion, PMSC may improve the healing of wounds in CLI patients,

Safety and efficacy of UC-MSC infusion in patients with decompensated liver cirrhosis have been reported in a 1-year follow-up study. There were no significant side effects or complications and there was a significant reduction in the volume of ascites and improvement in liver function, as indicated by the increase of serum albumin levels and a decrease in total serum

Therapeutic effects of PMSC transplantation in MS patients have been evaluated in different studies. Intravenous infusion of UC-MSC appears to be safe and well tolerated in patients with MS, and the overall symptoms of treated patients remained stable or improved compared to the control group [105]. In another clinical trial, patients with relapsing-remitting MS or with secondary progressive MS randomly received PMSC

OA affecting the hip can mean, in many cases, the need for a total hip replacement (THR). A frequent side effect of THR is a gluteus medius injury. PMSC administered directly to the injured muscle during surgery have demonstrated their safety and efficacy inducing a greater increase in the gluteus medius muscle strength than placebo, and a significant improvement

Safety of the intravenous administration of PMSC (PDA001) to moderate-to-severe Crohn's disease patients unresponsive to other therapies has been demonstrated and some remission rates of the disease have been reported [107]. Likewise, in a randomized controlled clinical trial, intravenous injection of PMSC patient condition improved significantly allowing a significant reduction in steroid dosage. Additionally, several patients with anal fistula showed

1 PLX-PAD – Placenta eXpanded adherent stromal cells produced by PluriStem Ltd. PLX-PAD cells are derived from the

2 PDA-001 (previously cenplacel-L) is a placenta adherent cells-based therapy developed by Celgene Cellular Therapeutics (CCT, a subsidiary of Celgene Corporation) to treat autoimmune diseases. It is administered as an intravenous injection.

and most treated subjects had stable or decreasing Expanded Disability

and could allow for significant delays in events of amputation and death.

in muscle volume based on MRI. EudraCT Number: 2011-003934-16.

decidua of human placenta and are expanded using the company's 3D proprietary technology.

in the treatment of critical limb ischemia (CLI) has been cleared by

quality of life were observed in treated subjects [103].

240 Stromal Cells - Structure, Function, and Therapeutic Implications

study of PLX-PAD cells<sup>1</sup>

bilirubin levels [104].

Status Scale scores [106].

remarkable improvement [108].

(PDA-001)<sup>2</sup>

PMSC are promising candidates for use in regenerative medicine in humans. Cell therapy using PMSC is based mostly on three important characteristics of these types of cells: (i) their inherent reparative capacities or by secretion of paracrine factors; (ii) their homing and engraftment abilities; and (iii) their immune modulation capacities. However, clinical use of PMSC is still in its infancy and most of the trials are, to date, under development. Most studies of cellular therapy have been realized with autologous cells. Nevertheless, the use of patient's own cells has several limitations. First, there is a time-limiting factor as the expansion and quality control of autologous cells may require several weeks. Furthermore, the cells can show less potency due to inherent aging aspects and, even, certain characteristics of the subject may render autologous transplantation unfeasible as occurs in the case of elderly patients and those having a specific systemic disease such as diabetes. In contrast, allogeneic MSC have the potential to be mass-produced rapidly so they can be readily available and administered immediately. They can be obtained under more standardized and strictly validated conditions and probably reduce costs. To date, published data regarding reliability of treatment with PMSC indicate that the use of PMSC is safe and therefore there are already products "off-the-shelf." Although most clinical trials are ongoing or have no published results, there are some favorable data regarding to the efficacy of treatments with PMSC.

Stem cell nanomedicine is a very promising field that at the preclinical level has yielded very encouraging results. Treatment of certain pathologies can benefit from the use of scaffolds that provide a three-dimensional structure to give support to the cells, promoting their adhesion and growth, so definitely improving the engraftment and therefore the therapeutic results. Besides the use of cells as carriers of nanoparticles to deliver drugs inside the injured tissue and, even more, the possibility of stimulus-controlled release of the drug appears exciting.
