Will the maintenance of a Human Skeleton be possible in the future?

Written by Johnny Garcia and Edited by Amy Huynh

When crossing a structurally intact bridge, you trust that the components of the structure such as the steel, concrete, iron, and other materials are properly maintained. If your trust was well-placed, then each component of the bridge should accomplish its purpose and contribute toward the stability and strength of the bridge. Similarly, the health and function of our skeleton largely depends on its three main occurring compartments: bone, cartilage and stroma. In oversimplified terms, the bones provide stability and facilitate movement, cartilage provides flexibility and cushion in the bones, and the stroma of the bone marrow provides a location for the formation of blood cellular components [1]. Not surprisingly, organisms have evolved the capability to repair and reconstruct skeleton components through a process called skeletal regeneration. This process in humans becomes less effective with age or repetitive use, and the capability in humans is only modest compared to other vertebrates. In addition, healing bone fractures or wounded cartilage is not as simple as replacing a specific building block from a bridge because there is no current stock of cells to replace the wounded skeletal components. However, the ability to repair our skeletal components might improve due to a decade-long project led by scientists from the Stanford University School of Medicine in which they isolated a single type of cell called the human skeletal stem cell that can differentiate, or develop, into the three main components of the human skeleton [2].

On September 20, Cell published the article identifying the human skeletal stem cell (hSSC) with the lead author as Charles K.F. Chan, PhD, an assistant professor of surgery. The discovery and isolation of the hSSC provides a promising source of cells for regenerative treatment due to the cell’s uniqueness. Stem cells are precursors to various types of cells in the body, and each type of stem cell has a unique classification because hSSCs were shown to have the remarkable potential to develop into different cell types, which is also referred to as being multipotent. The hSSC was also shown to maintain its intact state while going through multiple cycles of cell division, confirming the ability of self-renewal, which is another hallmark quality of a stem cell [3]. However, unlike other current stem cells that have been identified throughout the human body, the development of hSSCs is restricted to cells associated with the skeleton. Therefore, the hSSC is tissue-specific and can only develop into cells for cartilage, stroma, and the bone [3].

Such a unique cell might sound hard to miss, yet the quest to identify the precursor cell of the skeleton became a bioinformatics challenge due to the uncharacterized proteins on its surface in comparison to its mouse counterpart [2]. Previous findings identified the mouse skeletal stem cell (mSSC) and characterized its surface proteins, referred to as markers, to facilitate the isolation of these cells through a technology called fluorescence-activated cell sorting (FACS) [4]. As a brief introduction, FACS is a specialized type of flow cytometry, meaning that the technique uses the flow of a buffer solution to pass individual cells through a beam of a laser. From the scattered light reaching the detectors, researchers can categorize cells based on their size and internal composition [5]. Some similar cell types between different species can share unique cell surface markers, and thus, researchers believed that the characterization of the mSSC from using FACS might be shared with the human skeletal cell. However, researchers did not identify a unique human cell that shared the same FACS characterization of the mSSC. Instead, they discovered a variety of human cells that shared the mSSC surface markers in the femoral growth plates.

As a result, the researchers focused on identifying cells with the highest similarity in gene expression to the mouse skeleton stem cell using a 17-week human fetal femur in order to find the best cell candidate. Eventually, the specific fetal growth plate cells that expressed a high similarity of gene expression to their mouse counterpart were identified. Once the researchers confirmed the hallmark qualities of a multipotent and self-renewing cell, they were able to identify the unique fetal growth plate cell as the human skeletal stem cell [2].

Bone fractures, joint injuries, and cartilage issues such as arthritis can potentially be treated by regenerative treatments through cell transplantation. Human skeletal stem cells are more likely to be clinically effective due their tissue-specificity unlike induced pluripotent stem cells (iPSC) or embryonic stem cells (ESCs) that have a high risk of tumor formation [6]. Ultimately, the researchers hope to use the human skeletal stem cell in clinical therapy to improve skeletal regeneration.

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