BACKGROUND:  Human hematopoietic stem cells (HSCs) hold great potential for cellular transplantation medicine for the treatment of cancers, blood disorders, and immunodeficiencies. However, HSCs cannot currently be maintained or expanded in culture, which is a limiting factor since the quantity of HSCs in more accessible sources such as from cord blood or human donors is low. Likewise, it has not been possible to derive functional human HSCs from embryonic stem cells (ESCs) or patient-specific induced pluripotent stem cells without retroviral transduction with transcription regulators or by using stroma lines that are of mouse origin, both of which present contamination issues. In order to facilitate HSC expansion or de novo generation in culture, it is imperative to understand the mechanisms of how HSCs are specified and maintained in vivo in their native microenvironments. In addition, establishment of conditions where HSCs can be cultured without animal stroma or retroviral manipulation is also critical.

INNOVATION:  Researchers from the UCLA have established novel human stroma cell lines that are derived from human embryonic and fetal hematopoietic sites. These novel cell lines can be divided into two categories - supportive and non-supportive cell lines. Supportive cell lines have been found to support the in vitro expansion of multipotent hematopoietic progenitors and were also shown to have the capacity to expand human stem or progenitor cells up to 100,000-fold during a 10 week culture. In addition, the supportive lines have the ability to promote specification of ESCs into hematopoietic progenitors and expand them into culture. The non-supportive cell lines were found to be capable of promoting differentiation of hematopoietic progenitors.

POTENTIAL APPLICATIONS 

• Stem cell therapies
• Transplantation medicine
• Model to study cell development and maintenance

ADVANTAGES

• Does not use animal cell lines
• Does not use retroviral manipulation
• Can be cultured for >40 passages without senescing

DEVELOPMENT-TO-DATE:  Human-derived human stroma cell lines that support the long-term expansion of multipotent hematopoietic progenitors in vitro have been established. These cell lines provide a way in which to expand HSCs in culture. The cell lines are currently being phenotyped and the mechanism by which they support HSC multipotentiality is being investigated.

Reference: UCLA Case No. 2009-006