Treatments

**149**

**Chapter 7**

*and Irina Kerkis*

**Abstract**

**1. Introduction**

Alternative Immune-

Mediated-Based Methods in the

*Vivian Gonzaga, Bruna Policiquio, Cristiane Wenceslau* 

latory property and are candidates for efficient supporting AA therapy.

immune-mediated aplastic anemia, paracrine effects, immunomodulation

interferon-gamma (IFN-γ) and transformed growth factor (TGF) [3–7].

>50 years are not eligible for transplant [8].

Aplastic anemia (AA) is a rare disease, caused by bone marrow (BM) aggression resulting in hypo or aplastic BM with precocious fat replacement and consequently to peripheral blood pancytopenia [1, 2]. The autoimmunity process in AA occurs due to the activation of the oligoclonal cytotoxic T cells that will lead the hematopoietic cells to apoptosis. Its triggering occurs by the imbalance between CD8 +, CD4 +, T-Helper (Th), Th type 1 (Th1), Th type 2 (Th2), Th17 type (Th17), Natural Killer (NK) and T-regulatory cells (Treg). Besides, there is also an abnormal production of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α),

For severe cases, immunosuppressive therapy is accepted as the first-line treatment option and the allogeneic transplantation of BM and hematopoietic stem cells (HSCs). However, 30–40% of patients with severe aplastic anemia (SAA) remain pancytopenia following the treatment. The transplant option still has a restricted number of compatibility between suitable donors. Additionally, patients aged

**Keywords:** allogeneic transplant, mesenchymal stem cell,

Acquired aplastic anemia (AA) is characterized by partial or total bone marrow (BM) destruction resulting in pancytopenia. Most of the acquired AA is the result of autoimmune condition the imbalance between T-regulatory cells (Treg), abnormal cytokines production and cytotoxic T cells activation, leading to the hematopoietic stem cells (HSCs) death. The first-line treatment is given by HSC transplant, but some patients did not respond to the treatment. Therefore, new technologies need to treat AA nonresponder patients. Studies are in progress to test the efficacy of stem cell-based therapeutic as mesenchymal stem cells (MSCs), which confer low immunogenicity and are reliable allogeneic transplants in refractory severe AA cases. Furthermore, MSCs comprise the BM stromal niche and have an important role in supporting hematopoiesis by secreting regulatory cytokines, providing stimulus to natural BM microenvironment. In addition, MSCs have immunomodu-

Aplastic Anemia Treatment
