Tachykinins and hematopoietic stem cell functions: implications in clinical disorders and tissue regeneration

Hematopoiesis is the process by which a limited number of hematopoietic stem cells (HSCs) maintain a functioning blood and immune system. In adults, hematopoiesis occurs in bone marrow and is supported by the microenvironment. The tachykinin family of peptides regulates hematopoiesis. Tachykinins can be released in bone marrow as neurotransmitters from innervating fibers, and from resident bone marrow cells. The hematopoietic effects by tachykinins involve four tachykinin genes, Tac1-Tac4. The latter is the most recently discovered member and encodes hemokinin-1, endokinin A, endokinin B, and two orphan peptides, endokinin C, and endokinin D. The alteration of normal hematopoietic functions by the tachykinins may result in the development of various pathologies. For example, Tac1 is involved in myelofibrosis and in leukemia, both of which are dysfunction of hematopoietic stem cells. A comprehensive understanding of dysfunctions caused by the tachykinins requires further research since other cells, such as stromal cells and factors including cytokines, chemokines, and endopeptidases, are involved in a network in which the tachykinins have critical roles. Studies into the properties and functions of tachykinins, the biology of their receptors, and related molecules would provide insights into the development of aging disorders, hematopoiesis, other dysfunction, and may also lead to the discovery of novel and effective clinical therapies. Controversies on applications for hematopoietic stem cells in regenerative medicine are discussed. Despite these controversies, a detailed understanding on how the bone marrow microenvironment maintains pluripotency of hematopoietic stem cells would be useful to manipulate the system to acquire specialized cells for tissue repair.